Traditional Chinese medicine composition for treating benign arrhythmia and preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating benign arrhythmia and a preparation method and application thereof. The traditional Chinese medicine composition comprises the following main active ingredients in parts by mass: 10-15 parts of coptis chinensis, 5-15 parts of American ginseng, 15-20 parts of salvia miltiorrhiza, 25-30 parts of humulus scandens, 5-10 parts of radix sophorae flavescentis, 10-15 parts of rhizoma nardostachyos, 10-15 parts of schisandra chinensis, 25-30 parts of magnetite and 5-10 parts of honey-fried licorice root. Animal experiments show that the traditional Chinese medicine composition can effectively improve cardiac functions and symptoms of arrhythmia of rats suffering from arrhythmia, relieve myocardial injury, relieve mitochondrial injury, reduce the content of an arrhythmia marker ET-1 in serum, increase the content of an arrhythmia marker NO in serum and increase expression of arrhythmia-related protein CX43. Therefore, the traditional Chinese medicine composition disclosed by the invention can be used for effectively treating the benign arrhythmia. Clinical tests show that the effective rate of the traditional Chinese medicine composition for treating premature beat can reach 86.67%, and the number of premature beat attacks can be obviously reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating benign arrhythmia, a preparation method thereof, and an application thereof. Background Art

[0002] Arrhythmia is one of the most common cardiovascular diseases. Arrhythmia is generally divided into malignant, latent malignant, and benign. Premature beats (extrasystole) are the most common benign arrhythmia, which are divided into atrial, junctional, and ventricular types according to different ectopic pacemaker points. Generally, no drug treatment is required; however, some patients experience symptoms such as palpitations, chest tightness, and fatigue, which affect sleep, daily life, and work, and drug intervention is needed. Currently, common anti-arrhythmic drugs such as beta blockers, sotalol, or propafenone and other western medicines can reduce the occurrence of premature beats. However, most western anti-arrhythmic drugs have great limitations in clinical treatment. For example, sotalol can cause sinus bradycardia and also bring certain airway toxicity; the negative inotropic effect of some beta blockers can lead to the emergence of congestive heart failure, constrict peripheral blood vessels, resulting in intermittent claudication, cold extremities, and tingling, and even skin necrosis; propafenone can induce ventricular tachycardia, and ventricular tachycardia is mostly in a single state, persistent and refractory, ineffective for electroshock treatment, and also presents digestive tract symptoms such as loss of appetite, nausea, and vomiting.

[0003] Traditional Chinese medicine plays an important role in the treatment of arrhythmia due to its multi-target effects and small side effects. Currently, there is still a lack of a traditional Chinese medicine composition that can effectively treat benign arrhythmia in clinical practice. Therefore, it is necessary to develop a traditional Chinese medicine composition that can effectively treat benign arrhythmia. Summary of the Invention

[0004] The first object of the present invention is to provide a traditional Chinese medicine composition for treating benign arrhythmia. The second object of the present invention is to provide a preparation method of the traditional Chinese medicine composition. The third object of the present invention is to provide an application of the traditional Chinese medicine composition.

[0005] According to the first aspect of the present invention, there is provided a traditional Chinese medicine composition for treating benign arrhythmia. Its main active ingredients in parts by mass include: 10 - 15 parts of Coptis chinensis, 5 - 15 parts of American ginseng, 15 - 20 parts of Salvia miltiorrhiza, 25 - 30 parts of Wuzhaolong, 5 - 10 parts of Sophora flavescens, 10 - 15 parts of Nardostachys jatamansi, 10 - 15 parts of Schisandra chinensis, 25 - 30 parts of Magnetitum, and 5 - 10 parts of roasted Glycyrrhiza uralensis.

[0006] The present invention aims at the pathogenesis of the mutual binding of "qi deficiency", "fire stagnation", and "blood stasis" in premature beats. Based on the three major treatment principles of "tonifying qi", "clearing fire", and "promoting blood circulation to remove stasis", starting from "tonifying qi and nourishing the heart, reducing fire and removing blood stasis", a self-made Sanshen Liansong formula (i.e., the traditional Chinese medicine composition of the present invention) is used for treatment.

[0007] In the formula, Coptis chinensis clears heat from the heart fire, dispels phlegm stasis and evil blood in the heart orifices, and helps the three ginsengs (i.e., American ginseng, Salvia miltiorrhiza, and Sophora flavescens) calm the heart and restore the pulse; American ginseng is bitter and cool and enters the heart, with the effects of supplementing qi and nourishing yin, clearing heat and promoting fluid production, being able to cool the heart and spleen fires, and supplementing qi in the chest. It is most suitable for those with qi deficiency and internal heat; Salvia miltiorrhiza promotes blood circulation to remove blood stasis, supplements the heart and stabilizes the mind, and is good at dredging the pericardium; Wuzhaolong functions to remove dampness and strengthen the spleen, tonify the middle qi to strengthen the root of the heart qi; Sophora flavescens clears heat and dries dampness, specifically treats the heart fire, purges heat and calms the heart, and restores the heart rhythm; Nardostachys jatamansi enters the heart meridian, nourishes the heart blood, stops palpitations and regularizes the rhythm; Magnetitum calms the shock and subdues yang, absorbs qi and tranquilizes the mind. Its heavy texture can calm the heart and relieve palpitations, and it also has the effect of supplementing the primordial qi and kidney qi; Schisandra chinensis tonifies the kidney and calms the heart, benefits qi and promotes fluid production, nourishes the heart body and removes internal heat; Prepared Licorice Root enters the heart meridian, supplements qi and relieves pain, and also harmonizes all the medicines.

[0008] In this formula, Coptis chinensis, American ginseng, and Salvia miltiorrhiza are the monarch drugs, mainly clearing and tonifying in combination, clearing the heart fire and supplementing the heart qi simultaneously, removing blood stasis and nourishing the heart blood in parallel; Wuzhaolong and Sophora flavescens are the ministerial drugs, clearing heat and purging fire and assisting with supplementing qi and tonifying the middle; Nardostachys jatamansi, Magnetitum, and Schisandra chinensis are the adjuvant drugs. Nardostachys jatamansi and Magnetitum have the functions of calming palpitations with heavy substances, restoring the pulse and regularizing the rhythm, and Schisandra chinensis nourishes the heart and relieves vexation. The three of them together improve symptoms such as insomnia and restlessness brought about by benign arrhythmia; Prepared Licorice Root is the guiding drug, harmonizing all the medicines, supplementing qi and relieving pain, and is an important drug for improving arrhythmia. All the medicines are used in combination, combining clearing and tonifying, tonifying the primordial qi, strengthening the five zang-organs, replenishing the heart body, thus promoting the circulation of qi and blood, removing stasis and stagnant fire, filling the vessels, and achieving the effects of restoring the rhythm and calming the mind.

[0009] The raw material sources of this formula are as follows:

[0010] Coptis chinensis: The dried rhizome of Coptis chinensis Franch., Coptis deltoidea C.Y. et Hsiao, or Coptis teeta Wall., plants of the genus Coptis in the family Ranunculaceae.

[0011] American ginseng: The root of Panax quinquefolium L., a plant of the genus Panax in the family Araliaceae.

[0012] Salvia miltiorrhiza: The dried root and rhizome of Salvia miltiorrhiza Bge., a plant of the genus Salvia in the family Lamiaceae.

[0013] Wuzhaolong: The root or branch of Ficus hirta Vahl., a plant of the genus Ficus in the family Moraceae.

[0014] Sophora flavescens: The dried root of Sophora flavescens Ait., a plant of the genus Sophora in the family Fabaceae.

[0015] Nardostachys jatamansi: The root and rhizome of Nardostachys chinensis Batal. or Nardostachys jatamansi DC., plants of the genus Nardostachys in the family Valerianaceae.

[0016] Schisandra chinensis: The ripe fruit of Schisandra chinensis (Turcz.) Baill. or Schisandra sphenanthera Rehd. et Wils., plants of the genus Schisandra in the family Schisandraceae.

[0017] Magnetitum: A mineral of the spinel group in the oxide class, mainly containing magnetite (Fe 3 O 4 ).

[0018] Fried Licorice Root: The processed product of licorice root.

[0019] In some embodiments, its main active ingredients by mass parts include: 10 parts of Coptis chinensis, 5 parts of American ginseng, 15 parts of Salvia miltiorrhiza, 30 parts of Pentapanax leschenaultii, 10 parts of Sophora flavescens, 15 parts of Nardostachys jatamansi, 10 parts of Schisandra chinensis, 30 parts of Magnetitum, and 10 parts of Fried Licorice Root.

[0020] In some embodiments, the dosage form of the traditional Chinese medicine composition is granule, decoction, powder or infusion.

[0021] In some embodiments, pharmaceutically acceptable excipients can also be added.

[0022] In some embodiments, the excipients are at least one of sustained-release agent, excipient, filler, binder, wetting agent, disintegrant, absorption promoter, adsorption carrier, surfactant, lubricant.

[0023] According to the second aspect of the present invention, there is provided a method for preparing the above traditional Chinese medicine composition. When the dosage form of the traditional Chinese medicine composition is decoction, the preparation method includes the following steps:

[0024] Wash the medicinal materials, add 8 - 10 times the weight parts of water, soak for 30 - 60 min, bring to a boil over high heat, then change to low heat and simmer for 30 - 45 min to obtain the juice; add 8 - 10 times the weight parts of water to the medicinal residues, decoct again to obtain the juice, and mix the juices obtained from the two decoctions to obtain the decoction.

[0025] According to the third aspect of the present invention, there is provided a method for preparing the above traditional Chinese medicine composition. When the dosage form of the traditional Chinese medicine composition is granule, the preparation method includes the following steps:

[0026] S1. Wash the medicinal materials, add 8 - 10 times the weight parts of water, soak for 30 - 60 min, bring to a boil over high heat, then change to low heat and simmer for 30 - 45 min to obtain the juice; add 8 - 10 times the weight parts of water to the medicinal residues, decoct again to obtain the juice, and mix the juices obtained from the two decoctions to obtain the medicinal juice;

[0027] S2. Filter the medicinal juice, concentrate it under reduced pressure at 70°C to a clear paste with a relative density of 1.08, add an equal volume of 80% ethanol-aqueous solution after cooling to room temperature, let it stand for 24 h after ethanol precipitation, take the supernatant, and concentrate it under reduced pressure at 70°C to a relative density of 1.2 to obtain a concentrated solution;

[0028] S3. Add an equal volume of water to the concentrated solution, stir and let it stand for 8 - 12 h, then concentrate it under reduced pressure at 70°C to a clear paste with a relative density of 1.38 - 1.40, add twice the amount of sucrose, an equal volume of 70% ethanol-aqueous solution and an equal volume of dextrin to the clear paste to make a soft material, and then make the soft material into granules with a 13-mesh medicinal sieve.

[0029] According to the fourth aspect of the present invention, there is provided the use of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating benign arrhythmia. Specifically, the benign arrhythmia includes premature beats and ventricular tachycardia.

[0030] According to the fifth aspect of the present invention, there is provided the use of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating palpitations, restlessness, chest tightness and pain, dizziness and tinnitus, insomnia and fatigue caused by qi and yin deficiency and upward disturbance of deficient fire.

[0031] The beneficial effects of the present invention include:

[0032] (1) The traditional Chinese medicine composition of the present invention benefits qi and promotes blood circulation, reduces fire and soothes the mind, and is used for palpitations, restlessness, chest tightness and pain, dizziness and tinnitus, insomnia and fatigue caused by qi and yin deficiency and upward disturbance of deficient fire, and those with ventricular premature beats, atrial premature beats, supraventricular tachycardia showing the above syndromes.

[0033] (2) Animal experiments show that the traditional Chinese medicine composition of the present invention can effectively improve the cardiac function and arrhythmia symptoms of arrhythmia rats, reduce myocardial damage, relieve mitochondrial damage in arrhythmia rats, reduce the content of arrhythmia marker ET-1 in the serum of arrhythmia rats, increase the content of arrhythmia marker NO in the serum of arrhythmia rats, and increase the expression of arrhythmia-related protein CX43 in arrhythmia rats. Thus, it is suggested that the traditional Chinese medicine composition of the present invention can effectively treat benign arrhythmia.

[0034] (3) Clinical trials show that the effective rate of the traditional Chinese medicine composition of the present invention in treating premature beats can reach 86.67%, and can significantly reduce the number of premature beat attacks.

[0035] (4) The traditional Chinese medicine composition of the present invention has a rapid onset for benign arrhythmia, can control arrhythmia for a long time, prevent recurrence, and can also prevent other adverse reactions such as concurrent severe cardiovascular events, and is safe with few adverse reactions. Description of the Drawings

[0036] Figure 1These are the electrocardiograms of rats in each group in the animal experiment of the present invention.

[0037] Figure 2 These are the HE pathological staining diagrams of myocardial injury repair of rats in each group in the animal experiment of the present invention.

[0038] Figure 3 These are the transmission electron micrographs of damaged mitochondria of rats in each group in the animal experiment of the present invention.

[0039] Figure 4 These are the immunohistochemical assay diagrams of arrhythmia index CX43 of rats in each group in the animal experiment of the present invention. Detailed implementation manners

[0040] The present invention will be further described in detail below in conjunction with specific embodiments. It should be noted that the following embodiments are only for better explaining the content of the present invention and do not limit the protection scope of the present invention. The process steps not disclosed in the embodiments are prior art. Unless otherwise specified, the following raw materials are all commercially available.

[0041] Embodiment 1

[0042] The traditional Chinese medicine decoction for treating benign arrhythmia in this embodiment is prepared from the following raw materials: 10 g of Coptis chinensis, 5 g of American ginseng, 15 g of Salvia miltiorrhiza, 30 g of Wuzhaolong, 10 g of Sophora flavescens, 15 g of Nardostachys jatamansi, 10 g of Schisandra chinensis, 30 g of Magnetitum, and 10 g of roasted Glycyrrhiza uralensis.

[0043] Its preparation method includes the following steps:

[0044] Wash the medicinal materials, add 10 times the weight of water to make the water level with the medicinal materials, soak for 30 min, bring to a boil over high heat, then change to low heat and simmer for 40 min to obtain the juice; add 8 times the weight of water to the medicinal residues to make the water level with the residues, decoct again to obtain the juice, and mix the juices obtained from the two decoctions to obtain the product.

[0045] The traditional Chinese medicine decoction prepared in this embodiment is one dose, and one dose is about 300 mL.

[0046] Embodiment 2

[0047] The traditional Chinese medicine granule for treating benign arrhythmia in this embodiment is prepared from the following raw materials: 10 g of Coptis chinensis, 5 g of American ginseng, 15 g of Salvia miltiorrhiza, 30 g of Wuzhaolong, 10 g of Sophora flavescens, 15 g of Nardostachys jatamansi, 10 g of Schisandra chinensis, 30 g of Magnetitum, and 10 g of roasted Glycyrrhiza uralensis.

[0048] Its preparation method includes the following steps:

[0049] S1. Wash the medicinal materials, add 10 times the weight of water to make the water level with the medicinal materials, soak for 30 min, bring to a boil over high heat, then change to low heat and simmer for 40 min to obtain the juice; add 8 times the weight of water to the medicinal residues to make the water level with the residues, decoct again to obtain the juice, and mix the juices obtained from the two decoctions to get the medicinal juice.

[0050] S2. Filter the medicinal juice obtained in step S1, concentrate it under reduced pressure at 70 °C to a clear paste with a relative density of 1.08, cool to room temperature, add an equal volume of 80% ethanol - aqueous solution, let it stand for 24 h after ethanol precipitation, take the supernatant, and concentrate it under reduced pressure at 70 °C to a relative density of 1.2 to obtain the concentrated solution.

[0051] S3. Add an equal amount of water to the concentrated solution obtained in step S2, stir and let it stand for 8 h, then concentrate it under reduced pressure at 70 °C to a clear paste with a relative density of 1.39. Add twice the amount of sucrose, an equal amount of 70% ethanol - aqueous solution and an equal amount of dextrin to the clear paste to make a soft material, and then use a 13 - mesh sieve to make the soft material into granules.

[0052] Next, in order to verify the therapeutic effect of the traditional Chinese medicine composition for treating benign arrhythmia (hereinafter referred to as Sanshen Liansong Formula) of the present invention on benign arrhythmia, the following animal experiments were carried out.

[0053] I. Experimental animals

[0054] 80 male SD rats (6 - 8 weeks old, weighing 220 - 250 g) were purchased from the Guangdong Provincial Medical Experimental Animal Center (Guangzhou, China, approval number: SCXK(YUE)2018 - 0002), and were raised in a SPF environment (temperature 22 ± 2 °C, humidity 50 ± 10%), with food and water provided.

[0055] II. Grouping

[0056] 80 male SD rats were randomly divided into four groups, with 20 rats in each group, and were respectively labeled as the normal group (Sham group), the model group (Model group), the Sanshen Liansong Formula group (SSLS group), and the positive drug metoprolol group (Metoprolol group).

[0057] III. Modeling method

[0058] An arrhythmia model induced by myocardial ischemia - reperfusion injury (MIRI) was established by ligating the left anterior descending coronary artery of rats to occlude ischemia for 30 min, and then removing the microvascular clamp for 2 h of reperfusion.

[0059] Rats in the model group, the Sanshen Liansong Formula group, and the positive drug metoprolol group were modeled according to the above - mentioned modeling method, and rats in the normal group were only threaded without ligation.

[0060] IV. Administration

[0061] On the day after model establishment, rats in the Sanshen Liansong formula group were intragastrically administered with the traditional Chinese medicine decoction prepared in Example 1 at a dosage of 13.125 g / kg / rat, twice a day for 2 consecutive weeks.

[0062] Rats in the positive drug metoprolol group were given metoprolol sustained-release tablets at a dosage of 50 mg / kg / rat, once a day for 2 consecutive weeks.

[0063] Rats in the normal group and the model group were intragastrically administered with 0.9% normal saline, 2 mL each time, once a day for 2 consecutive weeks.

[0064] V. Evaluation Indicators

[0065] 1. Cardiac function

[0066] After 2 weeks of drug administration, two-dimensional echocardiography was performed on anesthetized rats (3.0% isoflurane and 1.0 L / min O 2 flow rate) using a Vevo2100 ultrasound instrument equipped with an MS400 transducer. Calculate the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter.

[0067] 2. Electrocardiogram

[0068] After 2 weeks of drug administration, the rats were placed in a fume hood and anesthetized with an inhaled anesthetic (isoflurane) until they lost the pain response. According to the lead connection method of the electrocardiograph, the electrodes were attached to the forelimbs and hindlimbs of the rats at the specified positions. Start the electrocardiograph and record the electrocardiogram of the rats, observe the electrocardiogram waveform, and record parameters such as heart rate and rhythm.

[0069] 3. Myocardial injury

[0070] After 2 weeks of drug administration, the rats were subjected to abdominal aortic perfusion for tissue sampling to obtain tissue sections from the apex area. The tissue sections from the apex area were fixed with 4% formaldehyde for 24 h. After paraffin embedding, 4-μm sections were stained with hematoxylin for 3 min and eosin for 60 s at room temperature. The stained samples were evaluated using an Olympus BX50 fluorescence microscope (original magnification ×200).

[0071] 4. Mitochondrial injury

[0072] After 2 weeks of drug administration, the rats were sacrificed by abdominal aortic perfusion to obtain heart tissues. Heart tissues of 1 cm×1 cm×1 cm were fixed in 2.5% glutaraldehyde for 6 h, then fixed in 1% osmium tetroxide for 2 h. After dehydration with gradient ethanol, they were placed in 70% uranyl acetate for 3 h, followed by continued dehydration with gradient ethanol, impregnated with propylene oxide for 30 min, and soaked in pure epoxy resin for 2 h for successful embedding. Ultra-thin sections of 50-70 nm were prepared, stained with uranium and lead, and observed and photographed with a JEM1400 transmission electron microscope.

[0073] 5. Serum contents of arrhythmia indicators NO and ET-1

[0074] After 2 weeks of drug administration, the rats were sacrificed by abdominal aortic perfusion to obtain serum supernatant. Serum supernatant was taken and added with the corresponding enzyme-labeled antibodies, substrate solutions and termination solutions of the NO assay kit (A013-2-1, Nanjing Jiancheng Bioengineering Institute) and endothelin-1 (ET-1) kit (H093-1-1, Nanjing Jiancheng Bioengineering Institute). The absorbance value was detected by an enzyme-labeling instrument, and the contents of NO and ET-1 in the serum were calculated.

[0075] 6. Arrhythmia indicator CX43

[0076] After 2 weeks of drug administration, the rats were sacrificed by abdominal aortic perfusion to obtain paraffin sections from the apex area. Paraffin sections were taken, dewaxed and hydrated routinely, then added with CX43 primary antibody (AF0137, Affinity, dilution ratio 1:100), incubated overnight at 4 °C, then added with the corresponding secondary antibody and incubated at room temperature. Finally, stained with 3,3'-diaminobenzidine (DAB) and hematoxylin, observed and photographed under a microscope, and analyzed with Image J software.

[0077] VI. Statistical methods

[0078] The results were expressed as "mean ± standard error (Mean±S.E.M.)" and analyzed using SPSS 17.0 software. The differences between groups were compared by one-way analysis of variance (One-way ANOVA) (Dunnett's T3 without assuming homogeneity of variance). P<0.05 indicated that the difference was statistically significant.

[0079] VII. Experimental results

[0080] 1. Effects of Sanshen Liansong Recipe on cardiac function in arrhythmic rats

[0081] The effects of Sanshen Liansong Recipe on cardiac function in arrhythmic rats of each group are shown in Table 1.

[0082] Table 1 Effects of Sanshen Liansong Recipe on cardiac function in arrhythmic rats

[0083] Sham group Model group SSLS group Metoprolol group LVEF (%) 92.96±2.20 <![CDATA[48.28±3.49 ** > <![CDATA[73.79±5.10 && > 75.90±3.40 LVFS (%) 56.73±3.40 <![CDATA[19.42±1.82 ** > <![CDATA[43.44±3.05 && > 40.16±1.83 LVIDd (mm) 3.95±0.37 <![CDATA[6±0.25 ** > <![CDATA[4.67±0.21 && > 4.53±0.23 LVIDs (mm) 3.01±0.4 <![CDATA[5.83±0.32 ** > <![CDATA[4.41±0.32 && > 4.37±0.30

[0084] Note: In the table, ** indicates P < 0.01 compared with the Sham group; && indicates P < 0.01 compared with the Model group.

[0085] As can be seen from Table 1, compared with the Sham group, the LVEF and LVFS values of the rats in the Model group were significantly decreased (P < 0.01), and the LVIDd and LVIDs values were significantly increased (P < 0.01). Compared with the Model group, the LVEF and LVFS values of the rats in the SSLS group were significantly increased (P < 0.01), and the LVIDd and LVIDs values were significantly decreased (P < 0.01). This indicates that the traditional Chinese medicine composition of the present invention can effectively improve the cardiac function of arrhythmic rats.

[0086] 2. Effects of Sanshen Liansong Formula on Electrocardiogram of Arrhythmic Rats

[0087] The electrocardiograms of rats in each group are as Figure 1 shown. The results of the effects of Sanshen Liansong Formula on the electrocardiogram indexes of rats in each group are shown in Table 2.

[0088] Table 2 Results of the Effects of Sanshen Liansong Formula on Electrocardiogram Indexes of Rats in Each Group

[0089] Group Average heart rate (bpm) PR interval (ms) QRS interval (ms) QT interval (ms) Sham group 486.6±23.89 27.5±3.33 29.2±2.88 68.7±3.22 Model group <![CDATA[263.2±29.15 ** > <![CDATA[52.2±3.62 ** > <![CDATA[57.1±3.05 ** > <![CDATA[130.1±13.20 ** > SSLS group <![CDATA[447±15.17 && > <![CDATA[34.7±2.20 && > <![CDATA[30.37±2.68 && > <![CDATA[85.4±4.16 && > Metoprolol group 441.4±15.41 35.3±3.39 <![CDATA[37.1±2.22 ％ > 82.4±5.14

[0090] Note: In the table, ** indicates P < 0.01 compared with the Sham group; && indicates P < 0.01 compared with the Model group; % indicates P < 0.05 compared with the SSLS group.

[0091] From Figure 1 and Table 2, it can be seen that compared with the Sham group, the heart rate of the rats in the Model group was significantly decreased, and the PR interval, QRS interval and QT interval were significantly prolonged. Compared with the Model group, the heart rate of the rats in the SSLS group was significantly increased, and the PR interval, QRS interval and QT interval were significantly shortened. Compared with the SSLS group, the QRS interval of the rats in the Metoprolol group was slightly prolonged. This indicates that the traditional Chinese medicine composition of the present invention can effectively improve the arrhythmia symptoms of arrhythmic rats.

[0092] 3. Effects of Sanshen Liansong Formula on Myocardial Injury in Rats

[0093] The HE pathological staining diagrams of myocardial injury repair in rats in each group are as Figure 2 shown. From Figure 2It can be seen that the myocardial cells of the rats in the Sham group were normal in morphology, without edema, without inflammatory cell infiltration, with regular myofilament arrangement and uniform staining. Compared with the Sham group, the myocardial cells of the rats in the Model group were irregular in morphology, with darkly stained cell nuclei, inflammatory cell infiltration, and disordered myocardial fiber arrangement. Compared with the Model group, the myocardial cells in the SSLS group were regular in morphology and the myocardial fibers were arranged more regularly. The myocardial cells in the Metoprolol group were relatively normal in morphology and the myofilaments were arranged more regularly. This indicates that the traditional Chinese medicine composition of the present invention can effectively reduce myocardial injury in arrhythmic rats.

[0094] 4. Effects of Sanshen Liansong Formula on Mitochondrial Damage in Rats

[0095] The transmission electron micrographs of the damaged mitochondria of the rats in each group are as Figure 3 shown. It can be seen from Figure 3 that the myocardial fibers in the Sham group were arranged neatly, the mitochondria were in good morphology and regular arrangement. In the Model group, the mitochondria of the myocardial cells were arranged disorderly, with different shapes and sizes. Compared with the Model group, the myocardial fibers in the SSLS group were arranged more neatly, the mitochondria were in relatively regular morphology and the mitochondrial arrangement was more regular. The myocardial fibers in the Metoprolol group were arranged relatively neatly and the mitochondria were in relatively complete morphology. This indicates that the traditional Chinese medicine composition of the present invention can effectively relieve mitochondrial damage in arrhythmic rats.

[0096] 5. Effects of Sanshen Liansong Formula on Serum Contents of NO and ET-1, Arrhythmia Indexes in Rats

[0097] The results of the effects of Sanshen Liansong Formula on the serum contents of NO and ET-1 in rats are shown in Table 3.

[0098] Table 3 Results of the Effects of Sanshen Liansong Formula on Serum Contents of NO and ET-1 in Rats

[0099] Sham group Model group SSLS group Metoprolol group ET-1 (ng / ml) 8.23±2.05 <![CDATA[28.32±2.32 ** > <![CDATA[13.17±2.58 & > 14.47±3.00 NO (μmol / L) 83.04±8.12 <![CDATA[41.91±10.57 ** > <![CDATA[72.01±12.39 && > 78.10±8.05

[0100] Note: In the table, ** indicates P < 0.01 compared with the Sham group; & indicates P < 0.05 compared with the Model group; && indicates P < 0.01 compared with the Model group.

[0101] As can be seen from Table 3, compared with the Sham group, the serum content of ET-1 in the Model group was significantly increased (P < 0.01), and the serum content of NO was significantly decreased (P < 0.01); compared with the Model group, the serum content of ET-1 in the SSLS group was significantly decreased (P < 0.05), and the serum content of NO was significantly increased (P < 0.01). There was no significant difference in the serum contents of ET-1 and NO between the SSLS group and the Metoprolol group. This indicates that the traditional Chinese medicine composition of the present invention can effectively reduce the content of the arrhythmia marker ET-1 in the serum of arrhythmic rats, and at the same time effectively increase the content of the arrhythmia marker NO in the serum of arrhythmic rats.

[0102] 6. Effects of Sanshen Liansong Formula on the Arrhythmia Index CX43 in Rats

[0103] The immunohistochemical assay diagrams of the arrhythmia index CX43 in rats of each group are as Figure 4 shown. The results of the effects of Sanshen Liansong Formula on the expression of CX43 protein in rats are shown in Table 4.

[0104] Table 4 Results of the Effects of Sanshen Liansong Formula on the Expression of CX43 Protein in Rats

[0105] Sham group Model group SSLS group Metoprolol group CX43 (%) 62.3±3.87 <![CDATA[15.57±3.26 ** > <![CDATA[35.67±3.16 & > 38.27±3.12

[0106] Note: In the table, ** indicates P < 0.01 compared with the Sham group; & indicates P < 0.05 compared with the Model group.

[0107] As can be seen from Table 4, compared with the Sham group, the expression of CX43 in the Model group was significantly decreased (P < 0.01); compared with the Model group, the expression of CX43 in the SSLS group was significantly increased (P < 0.05). There was no significant difference in the expression of CX43 between the SSLS group and the Metoprolol group. This indicates that the traditional Chinese medicine composition of the present invention can effectively increase the expression of the arrhythmia-related protein CX43 in arrhythmic rats.

[0108] In summary, the traditional Chinese medicine composition of the present invention can effectively improve the cardiac function and arrhythmia symptoms of arrhythmic rats, reduce myocardial injury, relieve mitochondrial damage in arrhythmic rats, reduce the content of the arrhythmia marker ET-1 in the serum of arrhythmic rats, increase the content of the arrhythmia marker NO in the serum of arrhythmic rats, and increase the expression of the arrhythmia-related protein CX43 in arrhythmic rats. This suggests that the traditional Chinese medicine composition of the present invention can effectively treat benign arrhythmia.

[0109] In addition, in order to further verify the therapeutic effect of the traditional Chinese medicine composition (i.e., Sanshen Liansong Formula) for treating benign arrhythmia of the present invention on benign arrhythmia, the following clinical experiments were also conducted.

[0110] 1. Inclusion Criteria

[0111] (1) Aged ≥ 18 years and ≤ 80 years, regardless of gender;

[0112] (2) Ambulatory electrocardiogram indicates premature beats, and the diagnosis of premature beats conforms to the diagnostic criteria of Western medicine and traditional Chinese medicine;

[0113] (3) Willing to receive 4 weeks of drug treatment;

[0114] (4) Voluntarily participate, understand and sign the informed consent form.

[0115] 2. Exclusion criteria

[0116] (1) Potential malignant or malignant arrhythmias such as ventricular tachycardia, atrial fibrillation, etc.;

[0117] (2) Arrhythmias caused by severe valvular disease, congenital heart disease, pericardial disease and non - cardiac causes, or premature beats caused by liver, kidney and other important organ failure;

[0118] (3) Patients with severe primary diseases such as liver, kidney, hematopoietic system, etc., abnormal renal function, liver transaminase and alkaline phosphatase exceeding 3 times the upper limit of normal value, serum creatinine > 2mg / dl (176.82umol / L), blood potassium > 5.5mmol / L; cancer patients, patients with severe neuroendocrine system diseases and psychiatric patients, patients with malignant progressive diseases with an expected survival time of less than 1 year evaluated by clinicians;

[0119] (4) Patients with left ventricular outflow tract obstruction, myocarditis, large aneurysm, dissecting aneurysm, uncorrected valvular heart disease causing obvious hemodynamic changes;

[0120] (5) Patients planning to undergo cardiac ablation surgery in the near future, or those who have already undergone cardiac resynchronization therapy;

[0121] (6) Patients with allergic constitution, or those known to be allergic to the treatment drugs;

[0122] (7) Patients who participated in other drug clinical trials within 1 month;

[0123] (8) Pregnant or women planning to be pregnant and lactating women;

[0124] (9) Those who do not meet the inclusion criteria, refuse to sign the informed consent form, and those who, in the judgment of the researcher, cannot complete this study or cannot comply with the requirements of this study.

[0125] 3. Subject information

[0126] A total of 15 subjects were included, all of whom were patients with premature beats who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2024 to September 2024.

[0127] 4. Medication measures

[0128] All patients took the traditional Chinese medicine decoction prepared in Example 1 of the present invention, one dose per day, 300 mL per dose, and taken warm in two divided doses. The medication cycle was 4 weeks. No other medications were taken during the medication period.

[0129] 5. Efficacy evaluation

[0130] The clinical efficacy before and after treatment of the patients was compared, and the evaluation was based on the results of dynamic electrocardiogram examination. Marked effect: The number of premature beats in the dynamic electrocardiogram decreased by > 85%; Effective: The number of premature beats in the dynamic electrocardiogram decreased by 30% - 85%; Ineffective: The number of premature beats in the dynamic electrocardiogram decreased by < 30%. The total effective rate = (marked effect + effective) / total number of cases × 100%.

[0131] 6. Treatment results

[0132] The statistical results of the effective rate of the clinical efficacy of the Sanshen Liansong Formula and the number of premature beat attacks before and after treatment are shown in Table 5.

[0133] Table 5 Statistical results of the effective rate of the clinical efficacy of the Sanshen Liansong Formula and the number of premature beat attacks before and after treatment

[0134]

[0135]

[0136] Note: In the table, * indicates P < 0.05 compared with before treatment.

[0137] As can be seen from Table 5, the total effective rate of the Sanshen Liansong Formula in treating premature beats was 86.67%, and the number of premature beat attacks within 24 hours after treatment was significantly lower than that before treatment. This indicates that the effective rate of the traditional Chinese medicine composition of the present invention in treating premature beats can reach 86.67%, and can significantly reduce the number of premature beat attacks.

Claims

1. A Chinese medicine composition for treating benign arrhythmia, characterized in that: The main active ingredients include, by weight: 10-15 parts of coptis root, 5-15 parts of American ginseng, 15-20 parts of salvia miltiorrhiza, 25-30 parts of cinnamomum officinale, 5-10 parts of sophora flavescens, 10-15 parts of nardus strychnine, 10-15 parts of schisandra chinensis, 25-30 parts of magnetite and 5-10 parts of licorice root.

2. The Chinese medicine composition according to claim 1, characterized in that: The main active ingredients include, by weight: 10 parts of coptis root, 5 parts of American ginseng, 15 parts of salvia miltiorrhiza, 30 parts of cinnamon bark, 10 parts of sophora flavescens, 15 parts of nardus odoratus, 10 parts of schisandra chinensis, 30 parts of magnetite, and 10 parts of roasted liquorice.

3. The Chinese medicine composition according to claim 1 or 2, characterized in that: The dosage form of the Chinese medicine composition is granules, decoction, powder or instant preparation.

4. The Chinese medicine composition according to claim 1 or 2, characterized in that: Pharmaceutically acceptable excipients may also be added.

5. The Chinese medicine composition according to claim 4, characterized in that: The auxiliary material is at least one of a sustained-release agent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption promoter, an adsorption carrier, a surfactant, and a lubricant.

6. The method for preparing the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: When the dosage form of the Chinese medicine composition is a decoction, the preparation method thereof comprises the following steps: Wash the medicinal materials, add 8-10 times the weight of water, soak for 30-60 minutes, boil over high heat, then simmer over low heat for 30-45 minutes to obtain the juice; add 8-10 times the weight of water to the residue, boil again and obtain the juice, mix the juices obtained from the two decoctions to obtain the product.

7. The method for preparing the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: When the dosage form of the Chinese medicine composition is granules, the preparation method thereof comprises the following steps: S1. Wash the medicinal materials, add 8-10 times the weight of water, soak for 30-60 minutes, boil over high heat, and then slowly boil over low heat for 30-45 minutes to obtain juice; add 8-10 times the weight of water to the residue, boil again and obtain juice, mix the juices obtained by the two decoctions to obtain medicinal juice; S2, filter the juice, concentrate under reduced pressure at 70°C to a clear paste with a relative density of 1.08, cool to room temperature, add an equal amount of 80% ethanol-water solution by volume, let stand for 24 hours after ethanol precipitation, take the supernatant, and concentrate under reduced pressure at 70°C to a relative density of 1.2 to obtain a concentrated solution; S3. Add an equal amount of water to the concentrated solution, stir and let stand for 8-12 hours, then concentrate at 70°C under reduced pressure to a clear paste with a relative density of 1.38-1.40, add twice the amount of sucrose, an equal amount of 70% by volume ethanol-water solution and an equal amount of dextrin to the clear paste to make a soft material, and then use a 13-mesh sieve to granulate the soft material.

8. Use of the Chinese medicine composition according to any one of claims 1 to 5 in the preparation of a medicament for treating benign arrhythmia.

9. The use according to claim 8, characterized in that: The benign arrhythmias include premature beats and ventricular tachycardia.

10. Use of the Chinese medicine composition according to any one of claims 1 to 5 in the preparation of a medicine for treating palpitations and / or irritability and / or chest tightness and pain and / or dizziness, tinnitus and / or insomnia and fatigue caused by deficiency of both qi and yin and disturbance of virtual fire.

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