Traditional Chinese medicine composition for treating arrhythmia and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating arrhythmia and a preparation method thereof.The traditional Chinese medicine composition is prepared from radix pseudostellariae, radix ophiopogonis, schisandra chinensis, rhizoma nardostachyos, radix sophorae flavescentis, poria cocos, spina date seeds, radix curcumae, platycladi seeds and honey-fried licorice roots. S2, classification extraction; s3, fusing the extracting solution; s4, performing double purification; s5, performing low-temperature freeze-drying to prepare powder, introducing rhizoma nardostachyos and radix sophorae flavescentis as core law-regulating medicinal materials, forming a system of tonifying qi and yin, promoting blood circulation and regulating law, and calming heart and tranquilizing together with radix pseudostellariae and radix ophiopogonis, and experiments show that the composition can reduce the premature beat frequency of arrhythmia model rats by 68% and shorten the duration of atrial fibrillation by 72%, solves the problem of insufficient curative effect of traditional prescriptions on organic arrhythmia, and has a wide application prospect. 80% or above of impurities are removed through double purification, the stability of the preparation is remarkably improved, the test is accelerated for 6 months, the content change of effective components is smaller than or equal to 4%, thermosensitive components are prevented from being damaged by high temperature through low-temperature freeze-drying, and the stable curative effect is ensured.

Description

Technical Field

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

[0002] Cardiac arrhythmia refers to a condition caused by abnormalities in the heart's electrical conduction system, resulting in abnormal heart rate or rhythm. The core issue is a disorder in the heart's rhythm regulation function. A normal heart beats rhythmically at a frequency of about 60-100 beats per minute. However, in cases of arrhythmia, the heart may beat too fast, such as exceeding 100 beats per minute, which is called tachycardia. The heart may also beat too slow. A heart rate below 60 beats per minute is called bradycardia, or an irregular rhythm is called arrhythmia. These are related to abnormalities in the generation and conduction of cardiac electrical signals, such as sinoatrial node dysfunction, abnormalities in the heart's normal pacemaker, or obstructions in the atrioventricular node or intraventricular conduction pathways. These abnormalities alter the sequence or frequency of cardiac contraction and relaxation, affecting the heart's pumping function. Mild arrhythmias may have no significant impact, but severe arrhythmias can reduce the heart's pumping efficiency, leading to insufficient blood supply to the body's organs and causing symptoms such as dizziness, weakness, and chest tightness. In severe cases, they can even induce syncope, heart failure, or sudden death. Common types include sinus tachycardia, atrial fibrillation, premature ventricular contractions (PVCs), and atrioventricular block. Diagnosis relies on examinations such as electrocardiograms (ECG), and treatment needs to be adjusted according to the condition, with the aim of restoring a normal rhythm and maintaining normal cardiac pumping function.

[0003] Currently, Western medicine treatment mainly relies on antiarrhythmic drugs, such as propafenone, amiodarone, and radiofrequency ablation. However, these treatments have significant limitations: First, the side effects of these drugs are prominent. Class Ic drugs may worsen conduction block, and long-term use of Class III drugs can easily lead to thyroid dysfunction and pulmonary fibrosis. Furthermore, some drugs carry the risk of causing arrhythmias. Second, radiofrequency ablation is not always effective for complex arrhythmias associated with organic heart disease, with a recurrence rate of 15%-30% after the procedure. Third, Western medicine treatments often focus on "correcting the rhythm," making it difficult to improve the myocardial microenvironment and autonomic nerve function, and thus failing to fundamentally reduce the triggers for attacks. Summary of the Invention

[0004] The technical problems to be solved are: First, the side effects of drugs are prominent. Class Ic drugs may aggravate conduction block, and long-term use of Class III drugs can easily cause thyroid dysfunction and pulmonary fibrosis. In addition, some drugs have the risk of causing arrhythmia. Second, the efficacy of radiofrequency ablation for complex arrhythmias associated with organic heart disease is unstable, with a postoperative recurrence rate of 15%-30%. Third, Western medicine treatments mostly focus on "correcting rhythm" and are difficult to improve the myocardial microenvironment and autonomic nerve function, and cannot fundamentally reduce the triggers of attacks.

[0005] In view of the shortcomings of the prior art, the present invention provides a traditional Chinese medicine composition for treating arrhythmia and a preparation method thereof, thereby solving the technical problems mentioned in the background art.

[0006] Terminology and Declarations of this Invention: As used in this article, the articles “a,” “a kind,” and “the” include plural objects unless otherwise explicitly specified as a single (kind) object.

[0007] As used herein, numerical range: Unless otherwise expressly indicated, all ranges or ratios disclosed herein shall be understood to include any and all subranges or subratios contained herein. For example, a stated range or ratio of 1 to 30 shall be considered to be included between the minimum value of 1 and the maximum value of 30, and includes any subranges or subratios including endpoints, integers, decimals, or subranges or subratios consisting of integers or decimals.

[0008] As used herein, the terms “comprising,” “including,” “having,” “possessing,” “may,” “containing,” and their variations are open-ended conjunctions or terms that do not exclude the possibility of additional components or structures.

[0009] To achieve the above objectives, the present invention provides the following technical solution: The traditional Chinese medicine composition for treating arrhythmia includes Codonopsis pilosula, Ophiopogon japonicus, Schisandra chinensis, Nardostachys chinensis, Sophora flavescens, Poria cocos, Ziziphus jujuba var. spinosa, Curcuma longa, Platycladus orientalis seed, and Glycyrrhiza uralensis (processed).

[0010] The medicinal properties and effects of each herb in this invention are as follows: Codonopsis pilosula: Codonopsis pilosula has a sweet and slightly bitter taste and is neutral in nature. It enters the spleen and lung meridians and can replenish qi and promote body fluid production, nourish the heart and calm the mind. The codonopsis pilosula saponins it contains can enhance myocardial contractility and improve myocardial energy metabolism.

[0011] Ophiopogon japonicus: Ophiopogon japonicus is sweet and slightly bitter in taste and slightly cold in nature. It enters the heart, lung and stomach meridians. It can nourish yin and generate fluids, clear the heart and relieve irritability. Ophiopogon japonicus saponins can inhibit myocardial oxidative stress and stabilize myocardial cell membranes. Codonopsis pilosula and Ophiopogon japonicus are used together as the principal drugs to lay the foundation for "tonifying qi and nourishing yin" and improve myocardial blood supply and cell microenvironment.

[0012] Schisandra chinensis: Schisandra chinensis has a sour and sweet taste and is warm in nature. It enters the lung, heart and kidney meridians. It can astringe and consolidate, benefit qi and calm the mind. Schisandrin can regulate myocardial ion balance and prolong the effective refractory period.

[0013] Nardostachys jatamansi: Nardostachys jatamansi has a pungent and sweet taste and is warm in nature. It enters the spleen and stomach meridians and can regulate qi, relieve pain, and regulate heart rhythm. Valerianone can inhibit the excessive activation of myocardial sodium channels and reduce ectopic pacemaker impulses. Schisandra chinensis and Nardostachys jatamansi together assist the principal drug to enhance the effect of "tonifying qi and regulating rhythm".

[0014] Sophora flavescens: It is bitter and cold in nature, and enters the heart, liver, stomach, large intestine and bladder meridians. It can clear heat and dry dampness, calm the mind and relieve palpitations. Sophora flavescens alkaloids can slow down the heart rate and inhibit L-type calcium channels, and work synergistically with Nardostachys jatamansi to regulate heart rhythm.

[0015] Poria cocos: It has a sweet and bland taste and a neutral nature. It enters the heart, spleen and kidney meridians. It can promote diuresis and eliminate dampness, strengthen the spleen and calm the mind. Poria cocos polysaccharides can improve myocardial microcirculation, clear phlegm and turbidity obstruction, and reduce the inducing factors of arrhythmia.

[0016] Sour jujube seed: It has a sweet and sour taste and a neutral nature. It enters the heart and liver meridians and can nourish the heart and calm the mind, astringe sweat and promote body fluid production. Sour jujube seed saponins can inhibit sympathetic nerve excitation and improve sleep-related arrhythmias.

[0017] Turmeric: It has a bitter and cold taste and enters the liver, heart and gallbladder meridians. It can promote blood circulation, relieve pain, regulate qi and relieve depression. Curcumin can reduce blood viscosity, improve myocardial ischemia and relieve "phlegm and blood stasis obstructing the collaterals".

[0018] Arborvitae seed: It is sweet in taste and neutral in nature. It enters the heart, kidney and large intestine meridians. It can nourish the heart and calm the mind, moisten the intestines and relieve constipation. Arborvitae seed saponins can enhance central inhibition and prevent constipation from inducing arrhythmia.

[0019] Prepared licorice root: It is sweet in taste and neutral in nature. It enters the heart, lung, spleen and stomach meridians. It can tonify the spleen and replenish qi, and harmonize the effects of various medicines. Glycyrrhetinic acid can improve myocardial conduction function and moderate the bitter and cold nature of sophora flavescens and turmeric, ensuring that the medicinal properties of the prescription are mild.

[0020] In one possible implementation, the traditional Chinese medicine composition, by weight, includes 12-22 parts of Codonopsis pilosula, 15-25 parts of Ophiopogon japonicus, 8-15 parts of Schisandra chinensis, 6-12 parts of Nardostachys jatamansi, 10-20 parts of Sophora flavescens, 12-22 parts of Poria cocos, 15-25 parts of Ziziphus jujuba var. spinosa, 8-15 parts of Curcuma longa, 10-18 parts of Platycladus orientalis, and 6-12 parts of Glycyrrhiza uralensis (processed).

[0021] In one possible implementation, the traditional Chinese medicine composition includes 18 parts of Codonopsis pilosula, 20 parts of Ophiopogon japonicus, 12 parts of Schisandra chinensis, 9 parts of Nardostachys jatamansi, 15 parts of Sophora flavescens, 18 parts of Poria cocos, 20 parts of Ziziphus jujuba var. spinosa, 12 parts of Curcuma longa, 15 parts of Platycladus orientalis, and 9 parts of Glycyrrhiza uralensis (processed).

[0022] In one possible implementation, the traditional Chinese medicine composition for treating arrhythmia includes the following steps: S1. Sorting and pretreatment of medicinal materials: The medicinal materials are manually selected and impurities are removed. The nardostachys chinensis, jujube seed, and cypress seed are quickly rinsed with purified water at 30℃ and then dried at a low temperature of 40-45℃ for 2-3 hours. The remaining medicinal materials are dried in the shade at room temperature. All medicinal materials are crushed separately, mixed and passed through a 50-mesh sieve. S2. Categorized extraction: Nardostachys jatamansi, Ziziphus jujuba var. spinosa, and Platycladus orientalis seeds were used as the volatile component group and extracted by steam distillation. Codonopsis pilosula, Ophiopogon japonicus, Schisandra chinensis, Sophora flavescens, Poria cocos, Curcuma longa, and Glycyrrhiza uralensis were used as the water-soluble component group and extracted by enzymatic hydrolysis-ultrasound combined extraction. The extracts were collected separately. S3. Extraction fusion: Mix the distillate of the volatile component group with the concentrate of the water-soluble component group, add 0.4% potassium sorbate, and stir at 25°C for 15 minutes until completely dissolved; S4. Double purification: First, centrifuge the mixture at 3500 r / min for 12 minutes, take the supernatant, and then filter the supernatant through an ultrafiltration membrane with a molecular weight cutoff of 5000 Da. The operating temperature is 28-32℃ and the pressure is 0.2-0.25 MPa. S5. Low-temperature freeze-drying powder preparation: The ultrafiltrate is freeze-dried under vacuum with a pre-freezing temperature of -38℃ and a pre-freezing time of 4.5 hours, a sublimation drying temperature of -18 to -5℃ and a vacuum degree of 15-20Pa, and a desorption drying temperature of 26-30℃. The powder is then collected to obtain the traditional Chinese medicine composition.

[0023] In one possible implementation, during step S2, when extracting the volatile components by steam distillation, 9 times the amount of purified water is added, the mixture is heated to boiling and then kept at a gentle boil for 2.2 hours. The distillate is collected and refrigerated at 4°C for later use, while the residue is retained for the extraction of the water-soluble components.

[0024] In one possible implementation, during step S2, when the water-soluble components are extracted by enzymatic hydrolysis and ultrasonication, 11 times the amount of purified water is first added to adjust the pH to 5.2. Then, 1.0% of the total mass of the medicinal materials is added to a compound enzyme, with cellulase:pectinase = 2:1 and both enzyme activities being 100,000 U / g. The enzyme is then hydrolyzed at 46°C for 1.3 hours.

[0025] In one possible implementation, in step S2, the sample is ultrasonically treated with 320W for 25 minutes at an ultrasonic temperature of 50°C, then heated to 90°C to inactivate the enzyme for 16 minutes, filtered to obtain an extract, and concentrated under reduced pressure to a relative density of 1.10-1.15.

[0026] In one possible implementation, in step S3, the pH of the mixture is adjusted to 6.0-6.3 to avoid the acidic or alkaline environment from damaging the active ingredients.

[0027] In one possible implementation, in step S5, the total vacuum freeze-drying time is 17-19 hours, the moisture content of the dried powder is ≤2.8%, and it is passed through a 70-mesh sieve to ensure uniform particle size.

[0028] Beneficial effects compared to existing technologies: 1. In this regimen, Nardostachys jatamansi and Sophora flavescens are introduced as core rhythm-regulating herbs, forming a "qi-tonifying and yin-nourishing, blood-activating and rhythm-regulating, mind-calming and spirit-soothing" system with Codonopsis pilosula and Ophiopogon japonicus. Experiments show that this combination can reduce the number of premature beats by 68% and shorten the duration of atrial fibrillation by 72% in arrhythmia model rats, solving the problem of insufficient efficacy of traditional prescriptions for organic arrhythmias, and achieving synergistic and multi-target therapeutic effects. 2. In this method, the volatile components are extracted by steam distillation, which improves the valerone retention rate by 100% compared with the traditional decoction method; the water-soluble components are extracted by enzymatic hydrolysis and ultrasonic combined extraction, which improves the extraction rate of ginsenosides and matrine by 45%; double purification removes more than 80% of impurities, significantly improving the stability of the preparation. After 6 months of accelerated testing, the change in the content of effective ingredients is ≤4%; low-temperature freeze drying avoids high temperature damage to heat-sensitive components, ensuring stable efficacy. 3. All medicinal materials used in this regimen are listed in the Chinese Pharmacopoeia. Acute toxicity tests showed that the maximum tolerated dose in mice was 22 times the clinical dose, with no liver or kidney damage. The preparation can be formulated into various dosage forms to suit different conditions such as functional premature beats and coronary heart disease with atrial fibrillation. The recurrence rate in clinical follow-up was 40% lower than that in the Western medicine group. Detailed Implementation

[0029] The present invention will be further described below with reference to specific embodiments. The raw materials used in the following embodiments are all commercially available conventional raw materials; The technical solutions in this application are designed to address the problems described in the background, and are generally as follows: Example 1: This embodiment introduces a traditional Chinese medicine composition for treating arrhythmia, which, by weight, consists of 18 parts of Codonopsis pilosula, 20 parts of Ophiopogon japonicus, 12 parts of Schisandra chinensis, 9 parts of Nardostachys chinensis, 15 parts of Sophora flavescens, 18 parts of Poria cocos, 20 parts of Ziziphus jujuba var. spinosa, 12 parts of Curcuma longa, 15 parts of Platycladus orientalis, and 9 parts of Glycyrrhiza uralensis (processed).

[0030] The preparation method is as follows: S1. Sorting and pretreatment of medicinal materials: Pick out impurities, nardostachys jatamansi, jujube seed and cypress seed are quickly rinsed at 30℃ and then dried at 42℃ for 2.5 hours, the remaining medicinal materials are dried in the shade at room temperature, crushed and mixed and then passed through a 50-mesh sieve; S2. Classification and Extraction: Three medicinal herbs, including Nardostachys jatamansi, were extracted by steam distillation (9 times water, gentle boiling for 2.2 hours); seven medicinal herbs, including Codonopsis pilosula, were extracted by enzymatic hydrolysis and ultrasonic extraction (11 times water, pH 5.2, 1.0% compound enzyme, enzymatic hydrolysis at 46℃ for 1.3 hours, ultrasonication at 320W for 25 minutes). Nardostachys jatamansi and other herbs were distilled with 9 times water at gentle boiling for 2.2 hours, and the distillate was collected, leaving the residue. Codonopsis pilosula and other herbs were mixed with the residue, and 11 times water was added to adjust the pH to 5.2. Compound enzyme was added, and enzymatic hydrolysis was performed at 46℃ for 1.3 hours, followed by ultrasonication at 320W for 25 minutes, and then enzyme inactivation was performed at 90℃ for 16 minutes. The filtrate was concentrated to a relative density of 1.12. S3. Extraction fusion: The distillate and concentrate are fused together, and 0.4% potassium sorbate is added to adjust the pH to 6.2. The distillate is added to the concentrate at room temperature, 0.4% potassium sorbate is added and stirred well, and the pH is adjusted to 6.2 with sodium hydroxide. S4. Double purification: Centrifuge at 3500 r / min for 12 minutes, and filter the supernatant through a 5000 Da ultrafiltration membrane: Centrifuge the mixture at 3500 r / min for 12 minutes, and take the supernatant and filter it through a 5000 Da ultrafiltration membrane (30℃, 0.22 MPa). S5. Low-temperature freeze-drying powder preparation: Vacuum freeze-drying (pre-freezing at -38℃ for 4.5 hours, sublimation at -12℃ for 8 hours, and desorption at 28℃ for 5 hours), passing through a 70-mesh sieve to obtain powder (moisture content 2.3%): Ultrafiltrate is fed into a freeze dryer, pre-freezing at -38℃ for 4.5 hours, sublimation at -12℃ / 18Pa for 8 hours, desorption at 28℃ for 5 hours, pulverized and passed through a 70-mesh sieve to obtain powder with moisture content 2.3%.

[0031] Example 2: This embodiment introduces a traditional Chinese medicine composition for treating arrhythmia, which, by weight, consists of 12 parts of Codonopsis pilosula, 15 parts of Ophiopogon japonicus, 8 parts of Schisandra chinensis, 6 parts of Nardostachys jatamansi, 10 parts of Sophora flavescens, 12 parts of Poria cocos, 15 parts of Ziziphus jujuba var. spinosa, 8 parts of Curcuma longa, 10 parts of Platycladus orientalis, and 6 parts of Glycyrrhiza uralensis (processed).

[0032] The preparation method is as follows: S1. Sorting and pretreatment of medicinal materials: Same as in Example 1; S2. Classification and Extraction: Three medicinal herbs, including Nardostachys jatamansi, were extracted by steam distillation (9 times water, gentle boiling for 2.2 hours). Seven medicinal herbs, including Codonopsis pilosula, were extracted by enzymatic hydrolysis and ultrasonic extraction (11 times water, pH 5.2, 1.0% compound enzyme, 46℃ enzymatic hydrolysis for 1.3 hours, 320W ultrasonication for 25 minutes). Nardostachys jatamansi and other herbs were distilled with 9 times water at a gentle boil for 2.2 hours, and the distillate was collected, leaving the residue. Codonopsis pilosula and other herbs were mixed with the residue, and 11 times water was added to adjust the pH to 5.2. Compound enzyme was added, and the herbs were enzymatically hydrolyzed at 46℃ for 1.3 hours, ultrasonicated at 320W for 25 minutes, and then the enzyme was inactivated at 90℃ for 16 minutes. The filtrate was concentrated to a relative density of 1.10. S3-S4. Same as Example 1; S5. Low-temperature freeze-drying powder preparation: Vacuum freeze-drying (pre-freezing at -38℃ for 4.5 hours, sublimation at -12℃ for 8 hours, and desorption at 28℃ for 5 hours), passing through a 70-mesh sieve to obtain powder (moisture content 2.3%): The ultrafiltrate is fed into a freeze dryer, pre-freezing at -38℃ for 4.5 hours, sublimation at -12℃ / 18Pa for 8 hours, desorption at 28℃ for 5 hours, pulverized and passed through a 70-mesh sieve, and the water-soluble components are concentrated to a relative density of 1.10 to obtain powder with a moisture content of 2.5%.

[0033] Example 3: This embodiment introduces a traditional Chinese medicine composition for treating arrhythmia, which, by weight, consists of 22 parts of Codonopsis pilosula, 25 parts of Ophiopogon japonicus, 15 parts of Schisandra chinensis, 12 parts of Nardostachys jatamansi, 20 parts of Sophora flavescens, 22 parts of Poria cocos, 25 parts of Ziziphus jujuba var. spinosa, 15 parts of Curcuma longa, 18 parts of Platycladus orientalis, and 12 parts of Glycyrrhiza uralensis (processed).

[0034] The preparation method is as follows: S1. Sorting and pretreatment of medicinal materials: Pick out impurities, nigars, jujube seeds and cypress seeds are quickly rinsed at 30℃ and then dried at 42℃ for 3 hours, the remaining medicinal materials are dried in the shade at room temperature, crushed and mixed and then passed through a 50-mesh sieve. S2. Classification and Extraction: Three medicinal herbs, including Nardostachys jatamansi, were extracted by steam distillation (9 times water, gentle boiling for 2.2 hours). Seven medicinal herbs, including Codonopsis pilosula, were extracted by enzymatic hydrolysis and ultrasonic extraction (11 times water, pH 5.2, 1.0% compound enzyme, enzymatic hydrolysis at 46℃ for 1.3 hours, ultrasonication at 320W for 25 minutes). Nardostachys jatamansi and other herbs were distilled with 9 times water at gentle boiling for 2.2 hours, and the distillate was collected, leaving the residue. Codonopsis pilosula and other herbs were mixed with the residue, and 11 times water was added to adjust the pH to 5.2. Compound enzyme was added, and enzymatic hydrolysis was performed at 46℃ for 1.3 hours, followed by ultrasonication at 320W for 25 minutes, and then enzyme inactivation was performed at 90℃ for 16 minutes. The filtrate was concentrated to a relative density of 1.15. S3-S4. Same as Example 1; S5. Low-temperature freeze-drying powder preparation: Vacuum freeze-drying (pre-freezing at -38℃ for 4.5 hours, sublimation at -12℃ for 8 hours, and desorption at 28℃ for 5 hours), passing through a 70-mesh sieve to obtain powder (moisture content 2.3%): Ultrafiltrate is fed into a freeze dryer, pre-freezing at -38℃ for 4.5 hours, sublimation at -12℃ / 18Pa for 8 hours, desorption at 28℃ for 5 hours, pulverized and passed through a 70-mesh sieve to obtain powder with moisture content 2.5%.

[0035] Comparative Example 1: This comparative example is a composition with Nardostachys jatamansi and Sophora flavescens removed, containing 18 parts of Codonopsis pilosula, 20 parts of Ophiopogon japonicus, 12 parts of Schisandra chinensis, 18 parts of Poria cocos, 20 parts of Ziziphus jujuba var. spinosa, 12 parts of Curcuma longa, 15 parts of Platycladus orientalis, and 9 parts of Glycyrrhiza uralensis (processed).

[0036] The preparation method is the same as in Example 1.

[0037] Comparative Example 2 This comparative example is prepared by traditional decoction, and the composition of the medicinal materials is the same as in Example 1.

[0038] The preparation method is as follows: Mix all the medicinal materials, add 10 times the amount of purified water, soak for 30 minutes, boil, simmer for 2.5 hours, and filter to obtain the first decoction; add 8 times the amount of water to the dregs, simmer for 1.5 hours, and filter to obtain the second decoction; combine the decoctions, concentrate under reduced pressure at 60℃ to a relative density of 1.25, dry and pulverize at 60℃ to obtain powder.

[0039] Pharmacological efficacy experiment: Therapeutic effect on rats with arrhythmia Experimental animals: 140 SPF-grade SD rats, half male and half female, weighing 220-250g, were acclimatized for 1 week.

[0040] Model establishment: Atrial fibrillation model was established by tail vein injection of "calcium chloride-acetylcholine mixture (calcium chloride 10mg / kg + acetylcholine 0.1mg / kg)". After injection, ECG monitoring showed that the P wave disappeared and was replaced by the f wave, and the RR interval was absolutely irregular, which was considered as successful model establishment. After successful model establishment, the animals were randomly divided into 7 groups, with 20 animals in each group.

[0041] Normal control group: fed with basal feed, no medication; Model control group: After modeling, physiological saline was administered (by gavage, 10 mL / kg). Positive control group: Amiodarone (orally, 50 mg / kg) was administered after modeling. Example 1 group: The composition prepared in Example 1 was administered (by gavage, 2.0 g / kg). Example 2 group: The composition prepared in Example 2 was administered (by gavage, 2.0 g / kg); Comparative Example 1: The composition prepared in Comparative Example 1 was administered (by gavage, 2.0 g / kg). Comparative Example 2: The composition prepared in Comparative Example 2 was administered (by gavage, 2.0 g / kg). Administration and testing: Each group was administered the medication once daily by gavage for 4 consecutive weeks; 24 hours after the last administration, the following indicators were measured: Cardiac arrhythmia episodes: The biosignal acquisition system records 24-hour electrocardiograms and counts the number of premature beats and the duration of atrial fibrillation. Myocardial electrophysiological parameters: The heart was harvested via open-chest surgery, and action potential duration (APD50, APD90) and effective refractory period (ERP) were measured using glass microelectrode technology. Myocardial protection indicators: Blood was drawn from the abdominal aorta to detect serum troponin I (cTnI), superoxide dismutase (SOD), and malondialdehyde (MDA). Safety indicators: Serum ALT, AST, Scr, and BUN were measured, and liver and kidney function were observed.

[0042] Experimental results: Table 1: Arrhythmia occurrences (x±s, n=20) The core pathological manifestation of arrhythmia is abnormal excitation of ectopic pacemakers, leading to frequent premature beats and persistent atrial fibrillation. This experiment evaluated the regulatory effect of the composition on heart rhythm through 24-hour electrocardiogram monitoring: Compared with the normal control group, the model control group had 288±32 premature beats / 24h and atrial fibrillation duration of 46±8min / beat, while the normal control group had no arrhythmia. This indicates that the calcium chloride-acetylcholine mixture successfully induced an atrial fibrillation model in rats, and the model was effective (P<0.01).

[0043] Comparison between the example group and the model control group: The example group 1 showed the most significant effect on regulating heart rhythm, with the number of premature beats decreasing to 88±12 times / 24h (69.4% lower than the model group) and the duration of atrial fibrillation shortening to 11±4min / beat (76.1% lower than the model group). The differences were statistically significant (P<0.01). This result is related to the synergistic effect of valerone inhibiting sodium channels and matrine regulating calcium channels. At the same time, Codonopsis pilosula and Ophiopogon japonicus improved myocardial energy metabolism, providing a basis for heart rhythm stability.

[0044] Comparison between the Example Group and the Positive Control Group: The positive control group (amiodarone) had 96±15 premature beats / 24h and atrial fibrillation duration of 15±5min / beat. All indicators in the Example Group were better than those in the positive control group (P<0.05), indicating that the composition of the present invention is more effective in regulating heart rhythm.

[0045] Comparison between the comparative example group and the example group: The number of premature beats in the comparative example group (lacking Nardostachys jatamansi and Sophora flavescens) was 182±25 times / 24h, which was 106.8% higher than that in the example group (P<0.01), confirming that Nardostachys jatamansi and Sophora flavescens are the core medicinal materials for achieving the "regulation" effect. The number of premature beats in the comparative example group (traditional decoction method) was 148±22 times / 24h, which was 68.2% higher than that in the example group (P<0.01). This was because the traditional high-temperature decoction caused the loss rate of valerone in Nardostachys jatamansi to more than 60%, which greatly weakened the regulation effect, thus confirming the rationality of the classification extraction process of the present invention.

[0046] Table 2: Myocardial electrophysiological parameters (x±s, n=20) Myocardial electrophysiological disorders are the fundamental mechanism of arrhythmia. Shortening of APD50 and APD90 leads to increased excitability of cardiomyocytes, and shortening of ERP easily triggers reentry excitation, thereby inducing premature beats, atrial fibrillation and other arrhythmias. Comparison between the model control group and the normal control group: APD50, APD90 and ERP of the model control group were shortened by 32.5%, 26.5% and 25.8% respectively compared with the normal control group (P<0.01), indicating that the ion balance of cardiomyocytes in the model rats was disrupted and the electrophysiological function was significantly disordered, which is consistent with the pathological characteristics of arrhythmia.

[0047] Comparison between the Example Group and the Model Control Group: Example 1 group effectively improved myocardial electrophysiological indicators, with APD50 increasing to 116±10ms (36.5% higher than the model group), APD90 increasing to 170±12ms (25.0% higher than the model group), and ERP increasing to 181±11ms (28.4% higher than the model group). All indicators were close to the levels of the normal control group (P>0.05), confirming that the composition can restore normal electrophysiological function by regulating myocardial ion channels.

[0048] Comparison between the comparative example group and the example group: The APD50, APD90 and ERP of the comparative example group (lacking Nardostachys jatamansi and Sophora flavescens) were significantly lower than those of the example group (P<0.05). Due to the lack of key components for regulating ion channels, the electrophysiological abnormalities could not be corrected. The improvement effect of electrophysiological indicators in the comparative example group (traditional decoction method) was weaker than that in the example group (P<0.05). Due to the destruction of active ingredients such as Codonopsis pilosula saponins by high temperature, the improvement of myocardial cell metabolism was insufficient.

[0049] Table 3: Indicators of myocardial protection and safety (x±s, n=20) Myocardial injury and oxidative stress are important causes of arrhythmia. cTnI is a specific marker of myocardial cell injury, and its elevated level indicates myocardial damage. SOD is a key antioxidant enzyme, and MDA is a lipid peroxidation product. Together, they reflect the state of myocardial oxidative stress. ALT, AST, Scr, and BUN are used to assess drug safety.

[0050] Compared with the normal control group, the model control group showed a 1620.0% increase in serum cTnI, a 48.4% decrease in SOD, and a 282.4% increase in MDA (P<0.01), indicating that arrhythmia had caused myocardial damage and enhanced oxidative stress in rats.

[0051] Comparison between the Example Group and the Model Control Group: The Example 1 group showed the most significant cardioprotective effect, with serum cTnI decreasing to 0.31±0.07 ng / mL (64.0% lower than the model group), SOD increasing to 106±10 U / mgprot (60.6% higher than the model group), and MDA decreasing to 2.10±0.18 nmol / mgprot (56.1% lower than the model group) (P<0.01). This confirms that the composition can achieve cardioprotective effects by inhibiting oxidative stress and reducing cardiomyocyte apoptosis. Comparison between the Example group and the positive control group: The ALT level in the positive control group increased to 45±8 U / L (80.0% higher than that in the normal group), indicating a significant risk of liver damage; while the ALT level in Example 1 group was 26±5 U / L, which was not different from that in the normal control group (P>0.05), and the levels of Scr and BUN were normal, confirming that the safety of the composition of the present invention is significantly better than that of Western medicine.

[0052] Comparison between the comparative example group and the example group: The cTnI and MDA of the comparative example group (lacking Nardostachys jatamansi and Sophora flavescens) were higher than those of the example group (P<0.05), which led to continuous myocardial damage due to the lack of rhythm-regulating components; The SOD activity of the comparative example group (traditional decoction method) was lower than that of the example group (P<0.05), which was due to the high temperature destroying antioxidant components such as Ophiopogon japonicus saponins, thus weakening the myocardial protective effect.

[0053] Finally, it should be noted that the above embodiments are merely examples for clearly illustrating the present invention and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A traditional Chinese medicine composition for treating arrhythmia, characterized in that, It includes Codonopsis pilosula, Ophiopogon japonicus, Schisandra chinensis, Nardostachys jatamansi, Sophora flavescens, Poria cocos, Ziziphus jujuba var. spinosa, Curcuma longa, Platycladus orientalis seed, and Glycyrrhiza uralensis (processed).

2. The traditional Chinese medicine composition for treating arrhythmia as described in claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight, 12-22 parts of Codonopsis pilosula, 15-25 parts of Ophiopogon japonicus, 8-15 parts of Schisandra chinensis, 6-12 parts of Nardostachys jatamansi, 10-20 parts of Sophora flavescens, 12-22 parts of Poria cocos, 15-25 parts of Ziziphus jujuba var. spinosa, 8-15 parts of Curcuma longa, 10-18 parts of Platycladus orientalis, and 6-12 parts of Glycyrrhiza uralensis (processed).

3. The traditional Chinese medicine composition for treating arrhythmia as described in claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight, 18 parts of Codonopsis pilosula, 20 parts of Ophiopogon japonicus, 12 parts of Schisandra chinensis, 9 parts of Nardostachys jatamansi, 15 parts of Sophora flavescens, 18 parts of Poria cocos, 20 parts of Ziziphus jujuba var. spinosa, 12 parts of Curcuma longa, 15 parts of Platycladus orientalis, and 9 parts of Glycyrrhiza uralensis (processed).

4. The traditional Chinese medicine composition for treating arrhythmia as described in any one of claims 1 to 3, characterized in that, Includes the following steps: S1. Sorting and pretreatment of medicinal materials: The medicinal materials are manually selected and impurities are removed. The nardostachys chinensis, jujube seed, and cypress seed are quickly rinsed with purified water at 30℃ and then dried at a low temperature of 40-45℃ for 2-3 hours. The remaining medicinal materials are dried in the shade at room temperature. All medicinal materials are crushed separately, mixed and passed through a 50-mesh sieve. S2. Categorized extraction: Nardostachys jatamansi, Ziziphus jujuba var. spinosa, and Platycladus orientalis seeds were used as the volatile component group and extracted by steam distillation. Codonopsis pilosula, Ophiopogon japonicus, Schisandra chinensis, Sophora flavescens, Poria cocos, Curcuma longa, and Glycyrrhiza uralensis were used as the water-soluble component group and extracted by enzymatic hydrolysis-ultrasound combined extraction. The extracts were collected separately. S3. Extraction fusion: Mix the distillate of the volatile component group with the concentrate of the water-soluble component group, add 0.4% potassium sorbate, and stir at 25°C for 15 minutes until completely dissolved; S4. Double purification: First, centrifuge the mixture at 3500 r / min for 12 minutes, take the supernatant, and then filter the supernatant through an ultrafiltration membrane with a molecular weight cutoff of 5000 Da. The operating temperature is 28-32℃ and the pressure is 0.2-0.25 MPa. S5. Low-temperature freeze-drying powder preparation: The ultrafiltrate is freeze-dried under vacuum with a pre-freezing temperature of -38℃ and a pre-freezing time of 4.5 hours, a sublimation drying temperature of -18 to -5℃ and a vacuum degree of 15-20Pa, and a desorption drying temperature of 26-30℃. The powder is then collected to obtain the traditional Chinese medicine composition.

5. The traditional Chinese medicine composition for treating arrhythmia as described in claim 4, characterized in that, In step S2, when extracting the volatile components by steam distillation, add 9 times the amount of purified water, heat to boiling and maintain a gentle boil for 2.2 hours, collect the distillate and refrigerate at 4°C for later use, and retain the residue for extraction of the water-soluble components.

6. The traditional Chinese medicine composition for treating arrhythmia as described in claim 4, characterized in that, In step S2, during the enzymatic hydrolysis-ultrasonic extraction of water-soluble components, 11 times the amount of purified water is added first, the pH is adjusted to 5.2, and then 1.0% of the total mass of the medicinal materials is added as a compound enzyme. The ratio of cellulase to pectinase was 2:1, with an enzyme activity of 100,000 U / g, and the enzyme was hydrolyzed at 46℃ for 1.3 hours.

7. The traditional Chinese medicine composition for treating arrhythmia as described in claim 4, characterized in that, In step S2, ultrasonic treatment is performed at 320W for 25 minutes; The process involves ultrasonically heating the sample to 50°C, then raising the temperature to 90°C for 16 minutes to inactivate the enzyme. The resulting extract is then filtered and concentrated under reduced pressure to a relative density of 1.10-1.

15.

8. The traditional Chinese medicine composition for treating arrhythmia as described in claim 4, characterized in that, In step S3, the pH of the mixture is adjusted to 6.0-6.3 to avoid acidic or alkaline environments damaging the active ingredients.

9. The traditional Chinese medicine composition for treating arrhythmia as described in claim 4, characterized in that, In step S5, the total vacuum freeze-drying time is 17-19 hours. After drying, the moisture content of the powder is ≤2.8%, and it is passed through a 70-mesh sieve to ensure uniform particle size.

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