A composition for reducing cardiac electrical activity disorder and use thereof

Abstract

The application provides a compound combination for reducing cardiac electrical activity disorder and application thereof, wherein the compound combination comprises magnesium and ginsenoside. The compound combination of the application can effectively reduce the risk of arrhythmia and sudden cardiac death caused by ventricular depolarization and repolarization disorder induced by influenza, novel coronavirus infection, other types of viral, bacterial, fungal and other microbial infections, chronic inflammatory diseases, various stressors and the like, and can be used for preparing drugs, health products or functional foods with corresponding functions. The application also screens the optimal ratio of the compound combination through a computer myocardial electrophysiological model to ensure the synergistic protective effect.

Description

Invention Field This application pertains to the field of prevention and treatment of heart disease. Specifically, this application provides a composition for reducing cardiac electrical activity disturbances and its application. Background Technology Infections encompass a wide range of types caused by bacteria, viruses, fungi, and parasites, such as HIV, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Candida albicans. Classified by site, infections include respiratory tract infections, urinary tract infections, digestive tract infections, bone and joint infections, central nervous system infections, cardiovascular system infections, bloodstream infections, and reproductive system infections. These infections not only involve multiple bodily systems, such as the respiratory and cardiovascular systems, but also often trigger severe inflammatory responses, potentially leading to cardiac complications. While COVID-19 primarily affects the respiratory system, it can also cause serious cardiac complications such as myocardial damage and arrhythmias, posing a high risk to patients' lives.

[0001] Infection triggers local or systemic inflammatory responses in the body, leading to the release of cytokines. As part of the body's immune defense, a certain degree of inflammation is a natural response to disease and injury, helping to expel invading pathogens. However, if the inflammatory response persists or expands, it may lead to cardiovascular disease or other illnesses. Fatigue, lack of sleep, stress, trauma, sub-health conditions, cancer, and other chronic diseases can all trigger inflammatory responses and release cytokines to varying degrees. If the body's regulation of the inflammatory response is poor, it may affect other organs or even endanger life. For example, while COVID-19 primarily presents with respiratory symptoms, it can also lead to severe myocardial damage, resulting in complications including heart failure, cardiomyopathy, arrhythmias, acute heart failure, and sudden death.

[0002] Alterations in cardiac electrical activity can develop into QT prolongation (QTP) on an electrocardiogram, and even malignant arrhythmias. These alterations are influenced by factors such as changes in ion channel function, altered gene expression, genetic factors, and congenital susceptibility. Changes in ion channel function are often caused by drugs or substances that affect the QT interval. Cardiac ion channel expression is related to inflammatory factors and proteins released in systemic inflammatory responses, involving infections, stress, lack of sleep, fatigue, and various systemic diseases or sub-health states affecting multiple organ systems. Hereditary ion channel alterations include congenital ion channel disorders, such as long QT syndrome, Brugada syndrome, and catecholamine-sensitive polymorphic ventricular tachycardia (CPVT). Changes in susceptibility are related to electrolyte balance, the presence of organic heart disease, and environmental factors.

[0003] The causes of arrhythmia or sudden cardiac death induced by different disease states such as infection can involve many aspects, such as: (1) Some viruses, such as the novel coronavirus, enter the host cell receptor through angiotensin-converting enzyme 2 (ACE-2), and ACE-2 is highly expressed in cardiomyocytes, endothelial cells, fibroblasts and smooth muscle cells, which provides a basis for the virus to directly damage cardiomyocytes. (2) Many respiratory diseases or respiratory complications of some diseases cause alveolar gas exchange disorders, resulting in hypoxemia, affecting the oxygenation of cardiomyocytes, and causing calcium ions to flow into cardiomyocytes, leading to cardiomyocyte damage and greatly increasing the risk of death. (3) Hypoxia can also lead to the accumulation of metabolites, induce mitochondrial damage and oxidative stress, cause mitochondrial dysfunction and energy metabolism disorders in cardiomyocytes, thereby inducing electroremodeling, causing arrhythmia and sudden cardiac death. (4) Infection, cancer or other inflammatory response-related fever can activate the sympathetic nervous system, causing increased myocardial oxygen consumption and relative oxygen deficiency, further aggravating myocardial damage. (5) Cytokine storms and inflammatory responses increase myocardial cell damage or apoptosis, reduce coronary plaque stability, and significantly increase the risk of cardiovascular events. (6) Stress states such as fatigue, lack of sleep or sleep deprivation, trauma, and drastic emotional changes induce sustained excitation of the sympathetic nervous system and massive release of catecholamines, which can lead to increased blood pressure, coronary artery spasm, microcirculatory disturbances, reduced perfusion, arrhythmia, and even sudden cardiac death. Furthermore, the continuous tension of the vascular wall can stimulate cells near the vascular wall to further activate inflammation, forming a vicious cycle. (7) Viruses such as SARS-CoV-2, which are mediated by ACE-2, bind to ACE-2, causing ACE-2 downregulation, reducing the production of Ang 1-7 which has a vasodilatory effect, and weakening the cardioprotective effect. (8) Sub-health status, cardiovascular diseases and their risk factors, such as diabetes, obesity, and smoking, cause endothelial dysfunction or viral infection of vascular endothelial cells, leading to endothelial cell damage and apoptosis, loss of integrity and increased permeability, and promoting endothelial thrombosis. (9) Drugs used to treat microbial infections or cancer and their complications, including azithromycin, moxifloxacin, Paxlovid (nematradivir tablets / ritonavir tablets), doxorubicin, arsenic trioxide, cisapride, etc., can directly or indirectly increase the risk of arrhythmias, such as QT interval prolongation, torsades de pointes ventricular tachycardia and sudden cardiac death.

[0004] An electrocardiogram (ECG) is a record of the heart's electrical activity during the cardiac cycle. Different bands represent different stages of cardiac electrical conduction. The QT interval represents the total time taken for ventricular depolarization to complete repolarization, roughly corresponding to the crucial stage from the start of ventricular contraction to the completion of diastole. The normal QT interval is 0.36-0.44 seconds. Clinically, a QTP is generally considered to exist if the interval exceeds 0.45 seconds in men and 0.47 seconds in women. If QTP progresses further, it can induce a potentially fatal arrhythmia—torsades de pointes (TdP). If the arrhythmia persists or ventricular fibrillation (VF) occurs, symptoms of TdP can include syncope and sudden cardiac death (SCD). Statistics show that for every 10 ms increase in the QT interval, the risk of progressing to TdP increases by 5%-7%. It is generally believed that when the absolute QT interval is >500 ms, the risk of TdP is 2-3 times higher than in the general population, and the risk of sudden cardiac death is significantly increased. Both congenital and acquired susceptibility greatly increase these risks, such as congenital long QT syndrome, drug-induced QT prolongation, electrolyte disturbances (hypokalemia, hypocalcemia, hypomagnesemia), acid-base imbalance, certain structural heart diseases, myocardial ischemia, bradycardia, and female sex. If a patient has multiple conditions combined, especially in special populations, with complex conditions, or with combined medications, the risk of malignant arrhythmias or sudden death is even higher. Although existing treatments can alleviate cardiac complications to some extent, most only target specific symptoms and cannot fundamentally improve myocardial metabolism and overall cardiac electrical activity. For example, some antibiotics, antiviral drugs, and anti-inflammatory drugs, while treating infections, may increase the risk of QTP, thus exacerbating cardiac complications. Summary of the Invention

[0005] This invention proposes a compound combination containing magnesium and ginsenosides that can comprehensively regulate cardiac function, thereby more effectively preventing and treating cardiac complications. In this combination, magnesium ions provide a fundamental guarantee for cardiac electrical activity by antagonizing calcium ion influx and stabilizing cardiomyocyte excitability; while ginseng extract (whose active ingredient is ginsenosides) synergistically enhances the protective effect on the myocardium by improving myocardial energy metabolism and enhancing cellular hypoxia tolerance, working together with magnesium ions to strengthen the overall protective effect on the myocardium. Through this combination, cardiomyocyte metabolic and electrical activity disorders can be comprehensively improved from multiple angles and mechanisms, effectively reducing the risk of malignant arrhythmias and sudden cardiac death.

[0006] This invention provides a novel compound combination that can effectively prevent and improve myocardial cell energy metabolism disorders and cardiac electrical activity disorders caused by infection, fatigue, sleep deprivation, stress, trauma, cancer, etc., thereby reducing the risk of malignant arrhythmias and sudden cardiac death. Single components or formulations of different concentrations cannot achieve the comprehensive effects of this invention in terms of myocardial cell metabolism and electrophysiological function.

[0007] The present invention proposes a composition for reducing cardiac electrical activity disorders, characterized in that it comprises a magnesium salt and ginsenosides, wherein the weight ratio of magnesium in the magnesium salt to ginsenosides is 100:1 to 1:100.

[0008] Furthermore, the compound composition comprises magnesium and ginsenosides in a mass ratio of 40:1 to 1:40.

[0009] Furthermore, the compound composition comprises magnesium and ginsenosides in a mass ratio of 10:1 to 1:10. This application uses a computer-aided myocardial electrophysiology model to optimize the ratio of magnesium to ginsenosides. Based on human ventricular myocyte data, the model simulates the effects of the compounds on action potential duration (APD) and early afterdepolarization (EAD), determining the optimal mass ratio to be 10:1 to 1:1.

[0010] Furthermore, the magnesium is derived from the following magnesium components: magnesium carbonate, magnesium sulfate, magnesium chloride, magnesium gluconate, and combinations thereof with various anions.

[0011] Furthermore, the ginsenosides are derived from ginseng powder and ginseng extracts of different specifications.

[0012] On the other hand, the compound combination is used to reduce cardiac electrical activity disorders.

[0013] Furthermore, in the aforementioned application, the cardiac electrical activity disorder is an infection-induced cardiac electrical activity disorder.

[0014] Furthermore, the cardiac electrical activity disorder is a cardiac electrical activity disorder caused by a systemic inflammatory response.

[0015] Furthermore, the cardiac electrical activity disorder is caused by fatigue, insufficient or absent sleep, stress, sub-health state, severe or chronic disease state such as cancer.

[0016] Furthermore, the infection is a novel coronavirus infection.

[0017] Furthermore, the cardiac electrical activity disorder is electrocardiographic QTP or long QT syndrome (LQTS).

[0018] Furthermore, the cardiac electrical activity disorder is ventricular tachycardia.

[0019] Furthermore, the cardiac electrical activity disorder is torsades de pointes ventricular tachycardia.

[0020] Furthermore, the aforementioned cardiac electrical activity disorder is a form of sudden cardiac death.

[0021] In another aspect, the compound combination is an oral formulation, an injection, a topical formulation, or a spray.

[0022] Furthermore, the oral preparation is a capsule, oral liquid, powder, granule or tablet.

[0023] Furthermore, the injection is a liquid injection or a powder injection.

[0024] Furthermore, the application of the aforementioned compound combination in the preparation of functional foods.

[0025] Furthermore, the application of the aforementioned compound combination in the preparation of health products and pharmaceuticals.

[0026] In this application, the terms "novel compound combination" and "compound combination" have the same meaning and can be used interchangeably.

[0027] Each component in the compound combination in this application is equivalent to a compound existing as an individual component, a cation, an anion, or a chelate.

[0028] The components in the compound combination of this application can be prepared in the same compound composition; or they can be provided in the form of two or more separate combinations in the same package; or they can be packaged separately and used together; all combinations known in the art are applicable to this invention.

[0029] The dosage forms applicable in this application include, but are not limited to, oral formulations and injections. The compound formulations, preparations, and compound combination formulations of this application can be applied to any clinically acceptable specific dosage form, including but not limited to: tablets, capsules, oral liquids, injections, powder injections, topical preparations, sprays, etc. When different components of a compound combination are provided in the same package or in various packages, the dosage forms of the different components can be the same or different.

[0030] Depending on the dosage form used for preparation / application, various pharmaceutically acceptable excipients may be selected for the formulation, including but not limited to coating materials, solvents, solubilizers, binders, stabilizers, antioxidants, pH adjusters, and flavoring agents. These excipients can be selected by those skilled in the art based on pharmaceutical knowledge.

[0031] In addition to the excipients mentioned above, the formulations of this application may also include, either alone or simultaneously with, other known diseases, states, or therapies that cause increased local or overall inflammatory activity, systemic inflammatory response, massive release of cytokines, malignant arrhythmias, or sudden death, including but not limited to fatigue, sleep deprivation or absence, life events, etc.; other infectious diseases, such as viral infections like HIV, bacterial infections like Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, etc., fungal infections like Candida, and other pathogenic microorganism infections; other disease states that cause sub-health in humans, such as hypertension, diabetes, obesity, chronic respiratory diseases, etc.; and other drugs or therapies that reduce cardiac electrical activity disturbances, including but not limited to beta-blockers, sympathetic nerve blockers, such as propranolol, phenytoin sodium, reserpine, adrenaline, atropine, verapamil, sympathectomy, etc.

[0032] Infections and other medical conditions can increase the risk of arrhythmias (abnormal changes in heart rhythm or rate) or sudden cardiac death, especially when patients also have congenital or acquired predisposing factors. Once changes in cardiac electrical activity occur, most cases cannot be successfully treated; therefore, preventing malignant arrhythmias is crucial to avoiding or reducing the risk of sudden cardiac death.

[0033] The compound combination provided in this application can effectively prevent and improve myocardial cell energy metabolism disorders and cardiac electrical activity disorders caused by infection, fatigue, lack of sleep, stress, trauma, cancer, etc., thereby reducing the risk of malignant arrhythmias and sudden cardiac death. Single components or different concentration ratios cannot achieve the comprehensive effects of this invention in terms of myocardial cell metabolism and electrophysiological function.

[0034] 1. This invention avoids the disturbance of cardiac electrical activity caused by various inflammatory responses such as infection, thereby reducing the possibility of problems such as arrhythmia, tachycardia, and sudden cardiac death. 2. This invention preserves the efficacy of effectively preventing and treating various inflammatory states, such as infection.

[0035] 3. This invention can effectively prevent malignant arrhythmias or sudden death associated with different disease states in people with infections or other inflammatory states, those with congenital long QT syndrome or other underlying diseases, those taking other drugs that cause cardiac electrical activity disorders, or those with electrolyte imbalances (hypokalemia, hypocalcemia, hypomagnesemia), liver and kidney dysfunction, existing heart failure, left ventricular hypertrophy, myocardial infarction, or other heart diseases that make them prone to arrhythmias.

[0036] 4. The compound combination of this invention has a certain effect on improving the energy metabolism of myocardial cells and has a cardioprotective effect. The compound preparation containing each component is more suitable for middle-aged and elderly people or patients with heart disease.

[0037] 5. Women are at higher risk than men for TdP caused by various inflammatory states such as infection, and this invention provides more significant protection for female patients. Attached Figure Description

[0038] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0039] Figure 1 Examples of normal ECG in animals during experiments; Figure 2 Examples of TdP appearing in animals under inflammatory conditions during experiments; Figure 3 The incidence of torsades de pointes (TdP) in each group of experimental animals; Figure 4 The incidence of ventricular tachycardia (VT) in each group of experimental animals; Figure 5 This represents the percentage change in FPDc of human cardiomyocytes under different drug treatments.

[0040] Figure 6 This represents the percentage change in field potential amplitude (FPA) of human cardiomyocytes under different treatment groups.

[0041] Figure 7 This study compares the percentage incidence of arrhythmic events in human cardiomyocytes under different treatment groups. Detailed Implementation

[0042] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0043] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0044] The terms “comprising,” “including,” “having,” “containing,” etc., used in this document are all open-ended, meaning they include but are not limited to. The terms “first” and “second” used in this document are for descriptive purposes only, and features specified as “first” or “second” may explicitly or implicitly include at least one of those features.

[0045] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art; the experimental methods used are all conventional methods; and the equipment, apparatus, materials, reagents, etc., used are all commercially available.

[0046] Example 1 This embodiment provides a computer simulation method for screening the optimal ratio of magnesium carbonate to ginseng extract (Xi'an Tianyi Biotechnology Co., Ltd., with a total saponin content of 80%). This method establishes an electrophysiological model of cardiomyocytes to predict the effects of different ratios on cardiac electrophysiological parameters, providing a theoretical basis for subsequent experimental verification.

[0047] 1. Model Building The CiPAOrd framework, a cardiomyocyte electrophysiological model, is used. The model is based on human ventricular myocyte data and includes magnesium ions (Mg). 2+ The pharmacokinetic parameters of ginsenosides and ginsenosides.

[0048] Ion channel effect: Magnesium ions act as calcium channel antagonists, mimicking their role in stabilizing the membrane potential of cardiomyocytes; total ginsenosides (≥80%) affect the action potential duration (APD) and repolarization process by inhibiting L-type calcium current (I_{Ca,L}) and transient outward potassium current (I_{to}), while also protecting cardiomyocytes.

[0049] The mathematical expression introduces a current adjustment term that depends on the magnesium ion concentration:

[0050] Among them, K dMagnesium ion dissociation constant. Ca,Mg‌ The final output is the calcium channel transmembrane current, which is regulated by magnesium ion concentration. Ca‌ is the maximum conductivity of the calcium channel, m∞(V) is the steady-state activation gating variable of the calcium channel, and h(V) is the steady-state inactivation gating variable of the calcium channel.

[0051] Frequency dependence: The effect of the simulated compound on action potential duration (APD90) at stimulation frequencies of 0.5–3.0 Hz, using an exponential decay function:

[0052] Parameters k=0.25, C=55ms.

[0053] Magnesium ions reduce calcium influx by inhibiting L-type calcium channels. The mathematical model uses the Hodgkin-Huxley equation to describe the current-voltage relationship, and the magnesium ion inhibition effect is achieved by modifying the gating parameters. Ginsenosides affect the action potential repolarization process by regulating the activity of the sodium-potassium pump; their concentration effect is simulated using the Hill equation. Model validation uses single-component electrophysiological data reported in the literature.

[0054] 2. Screening Process Blood drug concentration simulation: Peak concentrations after oral administration of compounds were predicted using a PBPK model. Magnesium carbonate HED≈12.6 mg / kg, ginseng extract HED≈5.75 mg / kg. Simulated Cmax after a single dose in a 60 kg adult was performed. Magnesium carbonate Cmax = 15 μM (half-life t1 / 2 = 6 h), ginsenoside Cmax = 8 μM (t1 / 2 = 4 h).

[0055] The evaluation indicators use three core parameters: Action potential duration (APD90) shortening rate, target value ≥8%. Early afterdepolarization (EAD) incidence, target value ≤3%. Complex polar dispersion (TDR) reduction ≥15% The comprehensive score for each proportion is calculated using a multi-objective optimization algorithm. The scoring formula is as follows: Overall score = 0.4 × APD90 shortening rate / 8% + 0.4 × (1 - EAD incidence rate / 3%) + 0.2 × TDR reduction rate / 15% 3. The screening results are shown in Table 1.

[0056] Table 1

[0057] The raw material magnesium carbonate in the above experiment was replaced with other magnesium salts, and the experiment was conducted according to the above method. The results are shown in Table 2.

[0058] Table 2

[0059] Protective Effect of Compound Combinations in Example 2 1. Experimental Animals New Zealand rabbits (Large Ear White), half male and half female, 1.8 - 2.2 kg, purchased from Beijing Long'an Experimental Animal Breeding Center, 40 rabbits, Production License: SCXK(Beijing)2021 - 0014.

[0060] 2. Experimental Reagents Urethane, HPLC purity ≥ 99%, Shanghai Macklin Biochemical Co., Ltd., Catalog Number U820333, C14784717 (Batch Number).

[0061] Lipopolysaccharide (LPS, Lipopolysaccharides from Escherichia coli O127), CP grade, Sigma - Aldrich (USA), Catalog Number L4516, 0000185322 (Batch Number).

[0062] Magnesium carbonate, USP grade, Shanghai Macklin Biochemical Co., Ltd.

[0063] Ginseng extract (total saponins 80%), Shanxi Nanba Biotechnology Co., Ltd.

[0064] 3. Experimental Methods (1) Anesthesia and Preparation for Electrocardiogram Recording Use New Zealand rabbits for whole - animal ECG experiments. Select experimental rabbits with similar age, weight and evenly divided gender. Use Urethane for intraperitoneal injection anesthesia to ensure that the experimental rabbits maintain a stable anesthetic state throughout the experiment. Then shave the hair on the back and limbs of the rabbits, apply conductive paste on the electrode patches, and connect them to the limbs and chest of the rabbits respectively. After ensuring that the electrodes are firmly adhered, connect the wires to the BL - 420N biological signal acquisition and analysis system. Adjust the system parameters to ensure clear and stable signals, and prepare for electrocardiogram recording.

[0065] (2) Grouping The experimental rabbits are divided into the following groups according to different experimental treatments. The specific treatments for each group are shown in Table 3: Table 3

[0066] Note: The actual ratio of each group = mass of magnesium element (Mg) : mass of total ginseng saponins Among them, the modeling methods of the magnesium carbonate alone group, the ginseng extract alone group, the proportion test group 1, the proportion test group 2, the proportion test group 3, and the proportion test group 4 were the same as those of the inflammation model group.

[0067] (3) Observation indicators The following ECG indicators are mainly analyzed: HR, QTP, QTc, TdP, VT, etc.

[0068] (4) Experimental procedure Electrocardiogram (ECG) recording: The BL-420N biosignal acquisition and analysis system was used to continuously record ECG signals from the rabbits' bodies. The recording time points are as follows: a. Record ECG signals from the start of the experiment (0 hours) until 30 minutes after intraperitoneal injection of LPS.

[0069] b. Record ECG signals at 24 hours and 48 hours after intraperitoneal injection of LPS, for 30 minutes each time.

[0070] (5) Data processing The recorded electrical signal data was imported into an Excel spreadsheet for initial processing. Subsequently, GraphPad Prism 9.0 software was used for data analysis and chart creation.

[0071] 4. Results Figure 1 This is a recording of a normal ECG in a rabbit. New Zealand rabbits were anesthetized, and in vitro whole-animal ECG recordings were performed on a rabbit platform using a biosignal acquisition and analysis system. LPS was administered intraperitoneally at a dose of 100 µg / kg body weight, as a single dose. This is a normal ECG of a healthy animal, showing regular, smooth P waves, QRS complexes, and T waves.

[0072] Figure 2 The ECG waveform of TdP in rabbits after cardiac electrical activity disorder is ventricular tachycardia (VT), characterized by wide and bizarre QRS complexes, excessively fast heart rate, and a basically regular rhythm.

[0073] like Figure 3 and Figure 4 As shown, Figure 3 The incidence of torsades de pointes (TdP) in each group of experimental animals was statistically analyzed. Figure 4The incidence of ventricular tachycardia (VT) was statistically analyzed to evaluate the preventive effect of the compound combination of the present invention on lipopolysaccharide (LPS)-induced inflammatory cardiac electrical activity disturbances. Compared with the negative control group, the incidence of TdP and VT in the inflammation model group was significantly increased, reaching 10.43% and 16.53%, respectively, indicating the successful establishment of the LPS inflammation model. While magnesium carbonate or ginseng extract alone could affect the incidence of TdP and VT to some extent, their effects were limited and showed no statistically significant difference compared to the inflammation model group, indicating poor efficacy of monotherapy. Combining magnesium carbonate and ginseng extract in a specific ratio exhibited a significant synergistic antiarrhythmic effect. The ratio test groups 1 and 2 showed better effects than the monotherapy groups. Particularly noteworthy is that the ratio test group 1 showed the most significant effect, with the incidence of TdP decreasing to 3.47% and the incidence of VT decreasing to 6.09%, the lowest among all treatment groups, significantly superior to the inflammation model group and the monotherapy group. The efficacy of ratio test group 4 (TdP: 4.08%, VT: 6.97%) was also better than that of the single drug and most other ratio combination groups, and its VT incidence was at a low level among the combination groups, showing a good synergistic effect.

[0074] Example 3 MEA demonstrates the protective effect of the combination of compounds of this application against cardiac arrhythmias. 1. Test cells hiPSC-CMs, purchased from Airpu Regenerative Medicine.

[0075] 2. Experimental reagents Magnesium gluconate, USP grade, Aladdin Company, item number M112987, G2227247 (lot number).

[0076] Ginseng extract (80% total ginsenosides), Shanxi Nanba Biotechnology Co., Ltd.

[0077] LPS, CP grade, Sigma-Aldrich (USA), item number L4516, 0000185322 (lot number).

[0078] 3. Test Methods (1) Experimental grouping Cell samples were divided into the following groups according to different experimental treatments, and the specific treatments for each group (n=5) are as follows: Negative control group: basal culture medium was administered only.

[0079] Inflammation group: Inflammation was induced by treatment with 1 μg / mL LPS. (Inflammation following LPS treatment of cardiomyocytes is an acute inflammatory response characterized by the release of pro-inflammatory cytokines, cell damage, and electrophysiological dysfunction.) Compound combination protection group: In addition to the same LPS treatment as the inflammation group, the group was given a compound combination (with a magnesium to ginsenoside ratio of 6:1, and final concentrations of magnesium gluconate 414.6 μg / mL and ginseng extract 166.9 μg / mL). (2) Observation indicators The following field potential (FP) parameters are mainly analyzed: Field potential duration (FPD) Corrected field potential duration (FPDc) Field Potential Amplitude (FPA) Number of arrhythmias (3) Experimental procedure a. Cell inoculation Cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSC-CMs) were seeded in the electrode areas of the MEA chip to ensure 100% cell confluence and synchronized beating. The seeded cardiomyocyte monolayers were cultured according to the manufacturer's instructions at 37°C and 5% CO2 for 10-14 days to ensure full cell recovery and the initiation of stable beating.

[0080] b. Electrophysiological signal recording Electrophysiological signals of cultured cardiomyocytes were recorded using an MEA system (Maestro, Axion BioSystems, Atlanta, Georgia). The recording time points are as follows: Each group in the baseline state begins recording the field potential signal for 5 minutes (baseline).

[0081] Field potential signals were generated 0.5, 1, 1.5...3 hours after LPS-induced inflammation.

[0082] After protection with the compound combination, LPS induced the field potential signal after inflammation.

[0083] c. Data Acquisition and Analysis Offline analysis of field potential duration (FPD) data was performed using AxIS (Axion Biosystems) software. The beat rate dependence of FPD was corrected using the Fridericia formula, and the clinically relevant ΔQTc was calculated.

[0084] d. Elution and subsequent processing In MEA experiments, the culture medium is usually washed after drug treatment to remove excess drug and prevent residues from affecting subsequent electrophysiological signals.

[0085] e. Results Recording In the MEA dataset, drug-induced arrhythmias were classified, recorded, and analyzed based on action potentials and arrhythmia patterns. It was found that some drug-treated cells exhibited spontaneous arrhythmias.

[0086] 4. Results Figure 5 This study shows the percentage change in FPDc in human cardiomyocytes under different treatment groups. It was used to evaluate the protective effect of the compound combination. Compared with the negative control group, the inflammation group treatment led to a significant increase in FPDc, indicating that its use alone has the potential toxicity of prolonging repolarization and increasing the risk of arrhythmias. Furthermore, the percentage increase in FPDc in the compound combination protection group was 8.24%, which, although higher than the negative control, was significantly lower than the inflammation group, demonstrating that this compound combination can partially alleviate varanoscalin-induced cardiac electrical activity abnormalities.

[0087] Figure 6 This study presents the percentage changes in field potential amplitude (FPA) of human cardiomyocytes under different treatment groups. In the negative control group, the FPA change percentage was -0.63%, indicating that the electrical signal amplitude of cardiomyocytes is stable under normal physiological conditions. The FPA change percentage in the inflammation group significantly decreased to -28.89%, indicating that the inflammation model successfully induced inhibition or damage to the electrical signal function of cardiomyocytes, reflecting a weakening of electrical activity under pathological conditions. Most importantly, the FPA change percentage in the compound combination protection group was significantly lower than that in the inflammation model, at -8.57%.

[0088] Figure 7 This study compares the percentage incidence of arrhythmic events in human cardiomyocytes under different treatment groups. The incidence in the negative control group was extremely low at 2.99%. The incidence in the inflammation group increased sharply to 40.94%, indicating that the inflammation model significantly increased cardiac electrical instability and induced fatal arrhythmias. The compound combination protection group significantly reduced the incidence of arrhythmias to 7.69%.

[0089] Obviously, the above embodiments are merely illustrative examples for clear explanation 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 here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A composition for reducing cardiac electrical activity disturbances, characterized in that, It includes magnesium salts and ginsenosides, wherein the magnesium salt contains magnesium in a weight ratio of 100:1 to 1:100 to ginsenosides.

2. The composition according to claim 1, wherein the weight ratio of magnesium in the magnesium salt to ginsenoside in the composition is 40:1 to 1:

40.

3. The composition according to claim 2, wherein the weight ratio of magnesium in the magnesium salt to ginsenoside in the composition is 10:1 to 1:

10.

4. The composition according to any one of claims 1-3, characterized in that, The magnesium salt includes at least one of magnesium carbonate, magnesium sulfate, magnesium chloride, and magnesium gluconate.

5. The composition according to any one of claims 1-3, characterized in that, The ginsenosides in the composition are derived from ginseng powder and / or ginseng extract.

6. The use of the composition according to any one of claims 1-5 in the preparation of a medicament for reducing cardiac electrical activity disturbances.

7. The application according to claim 6, wherein the cardiac electrical activity disorder is an infection-induced cardiac electrical activity disorder.

8. The application according to claim 6, wherein the cardiac electrical activity disorder is a cardiac electrical activity disorder caused by a systemic inflammatory response.

9. The application according to claim 6, wherein the cardiac electrical activity disorder includes cardiac electrical activity disorders caused by fatigue, sleep deprivation or absence, stress, sub-health state, severe or chronic disease states such as cancer.

10. The application according to claim 7, wherein the infection is a novel coronavirus infection.

11. The application according to any one of claims 6-10, wherein the cardiac electrical activity disorder includes electrocardiographic QTP or long QT syndrome.

12. The application according to any one of claims 6-10, wherein the cardiac electrical activity disorder is ventricular tachycardia.

13. The application according to any one of claims 6-10, wherein the cardiac electrical activity disorder is torsades de pointes ventricular tachycardia.

14. The application according to any one of claims 6-10, wherein the cardiac electrical activity disorder is sudden cardiac death.

15. The application according to any one of claims 6-14, wherein the drug is an oral preparation, an injection, a topical preparation, or a spray.

16. The application according to claim 15, wherein the oral preparation is a capsule, oral liquid, powder, granule or tablet.

17. The application according to claim 15, wherein the injection is a liquid injection or a powder injection.

18. The use of the composition according to any one of claims 1-6 in the preparation of functional foods.

19. The use of the composition according to any one of claims 1-6 in the preparation of health products.

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