Antiarrhythmic compound double-layer sustained-release preparation

Abstract

This invention discloses a compound bilayer sustained-release formulation for treating arrhythmia, belonging to the field of pharmaceutical technology. The formulation uses two purified active monomers from natural plants as its core active components, employing a rapid-release and sustained-release bilayer structure design with strictly controlled dosages for each layer of active monomers. The two active monomers of this invention have clearly defined primary and secondary pharmacological functions, possessing both core targeted therapeutic efficacy and complementary secondary pharmacological effects. One component primarily regulates myocardial electrophysiology and intervenes in arrhythmias, while also exhibiting auxiliary activities such as coronary artery dilation and myocardial protection. The other component primarily functions for myocardial protection, microcirculation optimization, and myocardial damage repair, while also assisting in stabilizing heart rhythm. Furthermore, the first active monomer possesses dose-dependent cardiovascular pharmacological characteristics. This invention features a scientifically formulated, mild, and stable and sustained drug release, simultaneously achieving both rhythm regulation and myocardial protection. It solves the problems of existing formulations, such as single target, low safety, and limited therapeutic systems. The preparation process is simple and controllable, showing promising prospects for industrialization.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a compound preparation of active monomers of traditional Chinese medicine derived from natural plants, and more particularly to an oral bilayer sustained-release solid preparation for cardiovascular diseases that uses a rapid-release and sustained-release layered drug release process to improve atrial premature beats, ventricular premature beats, sinus tachycardia, and also has a cardioprotective effect. Background Technology

[0002] Cardiac arrhythmias are a common type of myocardial electrophysiological abnormality in the cardiovascular field, with atrial premature beats, ventricular premature beats, and sinus tachycardia being the most common subtypes. The pathogenesis of these diseases is closely related to autonomic nervous system dysregulation, abnormal myocardial ion channel function, impaired myocardial microcirculation perfusion, myocardial oxidative stress damage, and local inflammatory pathological changes. Patients often experience palpitations, chest tightness, fatigue, and other clinical discomforts. Recurrent episodes can continuously increase the pathological burden on the myocardium and reduce the patient's quality of life. Currently, drugs used clinically to intervene in this type of mild arrhythmia are mainly divided into three categories: chemical antiarrhythmic drugs, traditional Chinese medicine compound preparations, and natural plant monomer preparations. All existing products have certain limitations in their use.

[0003] Although chemical antiarrhythmic drugs have a rapid onset of action, their clinical safety window is relatively narrow. During medication, adverse cardiac reactions such as bradycardia and atrioventricular block are likely to occur, and there is also a potential risk of inducing new arrhythmias. Long-term continuous use can increase the metabolic burden on the liver and kidneys, and may affect multiple systems and produce toxic side effects. Long-term drug tolerance and applicable populations are significantly limited.

[0004] Currently available Chinese herbal compound preparations and natural plant monomer preparations mostly follow the traditional treatment approach of nourishing the heart and regulating the pulse, as well as regulating qi and blood. They generally suffer from slow onset of action, making rapid intervention in acute arrhythmias difficult. Many of these compound preparations have complex material bases or single-target active monomers, lacking a systematic explanation of their overall mechanism of action. Furthermore, most are conventional fast-release formulations, lacking stratified controlled-release design, resulting in significant fluctuations in blood drug concentrations and poor long-term stable regulation of heart rhythm. Simultaneously, most preparations only focus on regulating cardiac rhythm signs, generally lacking quantifiable cardioprotective effects, only meeting daily conditioning needs and failing to simultaneously achieve the dual therapeutic goals of rapid symptom intervention and repair of myocardial pathological damage.

[0005] Addressing the numerous limitations in the application of existing Chinese and Western medicines, this invention scientifically combines two purified active monomers from natural plants to prepare a bilayer sustained-release formulation with dual effects of antiarrhythmic and cardioprotective properties. This invention innovatively employs a layered formulation process with rapid onset of action and sustained-release, long-lasting, stable release. This not only rapidly improves the clinical and pathological manifestations of atrial premature beats, ventricular premature beats, and sinus tachycardia, but also simultaneously achieves cardiomyocyte protection and myocardial microenvironment repair. The formulation is mild and has high safety, effectively avoiding the drawbacks of a single mode of action of purely chemical myocardial depressants. Through bidirectional pharmacological complementarity of components, it stabilizes rhythm regulation while protecting myocardial function, overcoming the shortcomings of traditional Chinese medicine preparations such as slow onset and unstable efficacy. It possesses significant technological innovation and industrial application value. Summary of the Invention

[0006] This invention aims to overcome the shortcomings of existing technologies and provide a compound antiarrhythmic bilayer sustained-release formulation with scientific compatibility, excellent drug release performance, clear pharmacological mechanism, good drug safety, and dual effects of cardiac rhythm regulation and overall myocardial protection. It solves the technical problems of existing similar formulations, such as single therapeutic target, insufficient long-term regulatory ability, lack of myocardial damage repair effect, and high drug safety risk.

[0007] The antiarrhythmic compound bilayer sustained-release formulation of the present invention adopts a scientific formula with multiple pharmacologically active monomers and a bilayer sustained-release formulation process design. The components work synergistically and complement each other to enhance the effect, thereby stabilizing the heart rhythm, protecting the myocardium and improving the safety of medication. The overall technical solution is reasonable and highly applicable.

[0008] I. Active Ingredients and Formula Ratio This invention relates to a compound bilayer sustained-release formulation composed of an immediate-release layer and a sustained-release layer laminated together. The active ingredients are two purified natural plant monomers with antiarrhythmic effects. The formulation contains no chemically synthesized pharmaceutical active ingredients, nor does it contain any added hormones or cardiac glycosides or other stimulating substances. The dosage ratios of each active monomer layer in this invention, calculated as a single-dose formulation, are as follows: Immediate-release layer: first active monomer 22mg, second active monomer 20mg; Sustained-release layer: 8 mg of the first active monomer and 15 mg of the second active monomer; Total active ingredients in a single-dose finished product: 30mg of the first active monomer and 35mg of the second active monomer.

[0009] The dosage ratio design of this compound two-layer sustained-release formulation is based on the following: Both the immediate-release layer and the sustained-release layer of this formulation contain two active components, corydaline and total astragaloside. The specific dosage is set as follows: immediate-release layer: corydaline 22mg, total astragaloside 20mg; sustained-release layer: corydaline 8mg, total astragaloside 15mg.

[0010] During the development of arrhythmias, myocardial electrophysiological dysfunction and myocardial tissue damage coexist and influence each other. This invention's bilayer structure, with both active ingredients fully compounded, allows each layer to simultaneously exert a dual effect of rhythm regulation and myocardial function protection, maintaining a synergistic pharmacological system throughout the entire process, highly consistent with the overall pathological characteristics of the disease. Each active component exhibits typical dose-dependent pharmacodynamic characteristics: Corydaline can rapidly correct abnormal myocardial rhythm at relatively high doses and can stably regulate myocardial electrophysiological state at relatively low doses; total astragalosides can immediately antagonize myocardial stress injury at relatively high doses and can continuously optimize myocardial energy metabolism and stabilize myocardial physiological function at relatively low doses.

[0011] This formulation combines the pharmacokinetic and in vivo metabolic elimination patterns of the active ingredients, employing a gradient design with a high-dose immediate-release layer for rapid efficacy and a low-dose sustained-release layer for steady-state maintenance. This precisely regulates stable changes in blood drug concentration, balancing immediate clinical symptom control with long-term maintenance of myocardial physiological homeostasis. This dosage regimen is based on rigorous pharmacodynamic, pharmacokinetic, and clinicopathological design principles.

[0012] The excipients used in this invention are all conventional pharmaceutical excipients listed in the Pharmacopoeia of the People's Republic of China; the immediate-release layer excipients include fillers, disintegrants, binders, and lubricants, and the sustained-release layer excipients include hydrophilic skeleton sustained-release materials, fillers, binders, and lubricants. The selection and dosage of various excipients all comply with the conventional standards for industrial pharmaceutical preparation.

[0013] II. Preparation Process This invention employs a dual-layer independent tableting process to produce the finished product. The immediate-release layer and the sustained-release layer are independently molded and pressed in separate layers, with no cross-mixing between the two layers. The sustained-release layer utilizes a hydrophilic framework material to achieve stable, zero-order drug release through constant-temperature dissolution. The overall process is mature and stable, suitable for large-scale, continuous industrial production. The specific preparation steps are as follows: 1. Preparation of immediate-release layer granules: Weigh the active monomers and pharmaceutical excipients according to the prescription ratio, mix them evenly, add a suitable binder solution to prepare a soft material, granulate through a 100-mesh sieve, dry at 45~55℃ under constant pressure, granulate, add lubricant and mix evenly, and set aside. 2. Preparation of sustained-release layer particles: Weigh the active monomer and hydrophilic skeleton sustained-release excipients according to the formula ratio, mix them evenly to prepare a soft material, granulate it through a 100-mesh sieve, dry it at 45~55℃ under normal pressure, granulate it, add lubricant and mix it evenly, and set it aside. 3. Tableting: The prepared immediate-release granules and sustained-release granules are sequentially fed into a double-layer tablet press, and the tableting pressure is adjusted to 5~8kN. The layers are independently pressed and formed to obtain the compound antiarrhythmic double-layer sustained-release tablet product.

[0014] III. Pharmacological Mechanism 1. Independent pharmacological mechanism of action of the first active monomer (tetracycline) The first active monomer is the natural plant purified active component that plays the core antiarrhythmic role in the compound of this invention. The pharmacological mechanism of this component is clear. It is a multi-target cardiovascular active substance confirmed by multiple published studies. Its core targets are concentrated in the fields of myocardial electrophysiological regulation and cardiovascular circulation regulation.

[0015] This component plays a core and dominant role in regulating the homeostasis of multiple ion channels in myocardial cell membranes and correcting abnormal electrical activity in the myocardium. It can effectively inhibit the abnormal automaticity of ectopic excitation foci in the myocardium, block the reentrant excitation conduction pathway in the myocardium, regulate the electrophysiological conduction rhythm of the myocardium, and specifically improve the pathological state of arrhythmias such as atrial premature beats, ventricular premature beats, and sinus tachycardia.

[0016] Simultaneously, this component possesses pharmacological activities including dilating coronary arteries, increasing coronary perfusion blood flow, and improving myocardial microcirculation; it also exhibits a clear cardioprotective effect, reducing the degree of cell damage under myocardial ischemia pathology and inhibiting the progression of oxidative stress inflammatory damage. The cardiovascular pharmacological effects of this component show a certain dose-dependent characteristic. Within the therapeutic dose range used in this invention, its main effects are antiarrhythmic, coronary artery dilation, and positive cardioprotective effects; only under ultra-therapeutic high dose conditions does it exhibit a slight delay in atrioventricular conduction and a mild inhibition of myocardial contraction. At the level of autonomic nervous system regulation, this component can balance the homeostasis of sympathetic and vagal nerve functions, alleviate cardiac rhythm disorders caused by excessive sympathetic nerve excitation, stabilize the pacing physiological function of the sinoatrial node, and help improve the pathological state of tachycardia from the level of neuroregulation, thereby achieving overall balanced regulation of cardiac rhythm.

[0017] This active monomer has mild overall pharmacological properties within the clinical therapeutic dose range, has no adverse effects on normal myocardial physiological function, and poses no risk of inducing new arrhythmias.

[0018] 2. Independent pharmacological mechanism of action of the second active monomer (total astragalosides) The second active monomer acts primarily through the following pathways: maintaining myocardial cell membrane homeostasis, improving myocardial microcirculation perfusion, antagonizing oxidative inflammatory damage, and repairing myocardial micro-damage pathological changes.

[0019] This component can stabilize the integrity of the phospholipid bilayer structure of myocardial cell membranes, reduce the degree of electrophysiological heterogeneity dispersion of myocardial cells, reduce the basis for the formation of abnormal re-entry excitation of myocardium, and reduce the probability of recurrent arrhythmia from the pathological root cause level.

[0020] It can dilate coronary microresistance vessels, improve the overall microcirculation perfusion level of myocardial tissue, alleviate the pathophysiological changes of myocardial ischemia and hypoxia, and reduce secondary myocardial electrophysiological disorders induced by ischemic injury.

[0021] It can also enhance the activity of endogenous antioxidant enzymes in myocardial tissue, clear the accumulation of excess oxygen free radicals in myocardial tissue, inhibit the overexpression of local inflammatory factors in myocardium, reduce the continuous damage to myocardial cells caused by oxidative stress and inflammatory infiltration, and exert a basic myocardial protective effect.

[0022] This component, relying on its dual functions of protecting myocardial structure and regulating energy metabolism, can further gently improve the physiological state of myocardial contraction, enhance the ability of myocardial cells to tolerate hypoxia and pathological stress, and improve the overall pathophysiological abnormalities of myocardium caused by myocardial dysfunction; at the same time, it can stabilize the overall homeostasis of the myocardium, help reduce the probability of abnormal electrical excitation of the myocardium, and form a pharmacological response with the first active monomer.

[0023] 3. Synergistic mechanism of two monomers The two active monomers derived from natural plants are scientifically combined to form a multi-target closed-loop synergistic regulatory system with a clear division of primary and secondary functions of the core targets and complementary secondary pharmacological functions.

[0024] The first active monomer focuses on targeted correction of abnormal myocardial electrophysiological disorders and rapid control of arrhythmias, aiming to treat the symptoms. The second active monomer focuses on repairing myocardial pathological damage, improving the myocardial circulatory microenvironment, and stabilizing the physiological basis of the myocardium, aiming to treat the root cause. Together, they construct a synergistic system that treats both the symptoms and the root cause from two core dimensions: myocardial electrophysiological regulation and myocardial tissue structure repair.

[0025] Simultaneously, both active monomers possess auxiliary pharmacological effects of cardiomyocyte protection and coronary microcirculation regulation. These two types of pharmacological effects are superimposed and produce a synergistic gain, further enhancing the overall cardiomyocyte protection and coronary circulation improvement. Based on the synergistic and complementary pharmacological functions of the two monomers, the pharmacological limitations of using a single component alone can be effectively reduced, improving the comprehensiveness and completeness of the overall therapeutic effect.

[0026] (1) Complementary and synergistic effects on target sites: In this invention, myocardial ischemia, myocardial injury, myocardial energy metabolism disorder, and autonomic nervous system homeostasis imbalance are the core pathological chains that induce myocardial ion channel dysfunction, ectopic pacemaker activation, and consequently various premature beats and sinus tachycardia. Repeated arrhythmias can further aggravate myocardial metabolic load, exacerbate myocardial ischemia and damage, and form a vicious cycle. The first active monomer of this invention focuses on neural rhythm regulation and myocardial electrophysiological intervention to rapidly block the arrhythmia process; the second active monomer focuses on myocardial cell protection, microcirculation optimization, and pathological damage repair to eliminate the intrinsic pathological causes of repeated arrhythmias. The two active monomers do not overlap in their target sites and their efficacy pathways complement each other.

[0027] (2) Synergistic effect of regulation: Both active monomers have positive cardiovascular regulatory activity and exert synergistic effects through direct electrophysiological regulation and indirect homeostasis regulation. Compared with the application of a single monomer alone, the overall regulation efficiency of heart rhythm regularity is significantly improved.

[0028] (3) Pharmacological bias balance and buffer: The second active monomer has the inherent pharmacological effects of protecting myocardium, improving microcirculation and regulating myocardial physiological state. It can improve the blood supply conditions of the cardiac conduction system and the overall physiological function. It can effectively buffer the potential myocardial physiological inhibition bias of the first active monomer under overdose application conditions, make up for the shortcomings of the single active monomer alone, and keep the physiological functions of cardiac contraction and conduction always within the normal physiological balance range.

[0029] (4) Synergistic effect of drug release time gradient: The immediate-release layer of this formulation can quickly release two active components, immediately start the regulation of nerve rhythm and myocardial electrophysiological intervention, and meet the rapid intervention needs of acute arrhythmia; the sustained-release layer, through its long-term stable drug release characteristics, continuously maintains the effective blood drug concentration in the body, maintains the homeostasis of the autonomic nervous system and myocardial internal environment for a long time, and achieves the therapeutic goal of long-term prevention and control of recurrence.

[0030] 4. Mechanism of overall cardioprotection The finished formulation of this invention has a clear overall active cardioprotective pharmacological activity and can effectively antagonize the myocardial micro-damage pathological changes that occur secondary to the progression of arrhythmia.

[0031] The formulation as a whole can enhance the activity of superoxide dismutase in myocardial tissue, reduce the malondialdehyde content in myocardial tissue, and block the cascade damage process of myocardial oxidative stress; downregulate the abnormally high expression of inflammatory factors such as myocardial tumor necrosis factor-α, reduce local inflammatory infiltration damage in the myocardium, and maintain the structural and functional integrity of myocardial cell membranes in the long term; simultaneously improve the overall microcirculation perfusion status of the myocardium, continuously alleviate myocardial ischemia and hypoxia micro-damage, and eliminate the intrinsic causes of recurrent premature beats and sinus tachycardia from the pathological root level.

[0032] IV. Pharmacodynamic Experimental Studies 1. Experimental subject conditions Experimental animals: SPF-grade healthy male SD rats, weighing 180g-220g, were selected; the temperature of the breeding environment was controlled at 22℃-25℃, the relative humidity was 50%-60%, and the day and night were alternated in a 12-hour cycle. The experimental animals were allowed free access to food and water and were acclimatized for 3 days; the entire animal experiment was conducted in accordance with animal ethics guidelines.

[0033] Animal grouping: The experimental rats were randomly stratified and grouped according to their body weight. There was no statistically significant difference in body weight among the groups. A total of 6 groups were set up, with 12 rats in each group.

[0034] Modeling methods: A rat atrial premature beat pathological model was established by intravenous administration of calcium chloride; a rat ventricular premature beat pathological model was established by intravenous administration of barium chloride; and a rat sinus tachycardia pathological model was established by isoproterenol induction.

[0035] Dosing regimen: Each group of test samples was administered the clinically equivalent dose by gavage once a day at a fixed time for 7 consecutive days; the model control group was given an equal volume of physiological saline by gavage; 60 minutes after the last administration, the electrophysiological and myocardial biochemical indicators of each group of rats were uniformly measured.

[0036] Experimental group setup: 1) Model control group; 2) Chemical positive drug control group; 3) Marketed traditional Chinese medicine control group 4) Single-use group of the first active monomer; 5) Single-use group of the second active monomer; 6) Compound formulation group of the present invention Control group definition: The chemical positive control group used first-line non-selective antiarrhythmic chemical drugs in clinical practice; the marketed traditional Chinese medicine control group used similar marketed solid dosage forms for nourishing the heart and regulating the pulse.

[0037] Detection indicators: After drug administration intervention, the average sinus heart rate, atrial premature beat inhibition rate, ventricular premature beat inhibition rate, drug onset time, and duration of drug effect were recorded in each group of rats; myocardial oxidative stress and inflammation-related biochemical indicators were detected simultaneously.

[0038] Indicator definitions: Onset time is defined as the time from drug administration to the appearance of significant improvement in the electrophysiological indicators of rats; Duration of drug effect is defined as the duration of time after the drug takes effect and maintains an effective therapeutic effect.

[0039] Detection methods: Myocardial biochemical indicators were all detected using corresponding biochemical test kits, and were uniformly detected using enzyme-linked immunosorbent assay (ELISA) and colorimetric methods, respectively.

[0040] Statistical analysis: All experimental data were statistically analyzed using SPSS 26.0 data analysis software. Quantitative data were expressed as mean ± standard deviation, and P < 0.05 was used as the criterion for statistical significance of the data differences.

[0041] Test group Mean sinus rhythm (beats / min) Atrial premature beat suppression rate (%) Ventricular premature beat suppression rate (%) Onset time (min) Duration of drug effect Model control group 158.6±7.2 8.7 7.9 —— —— Chemical positive control group 105.2±6.3 58.4 52.0 28±3 6.1±0.4 Control group of marketed traditional Chinese medicines 126.5±6.8 32.6 28.3 55±4 6.8±0.7 First active monomer single-use group 109.7±5.8 59.6 53.1 30±3 6.5±0.6 Second active monomer single-use group 115.2±6.1 45.3 38.5 33±3 7.5±0.5 The compound of the present invention 89.4±4.3 87.5 77.8 25±3 11.8±0.7 Experimental results show that the compound preparation of this invention has a better overall intervention effect than the model control group, the two monomer single-use groups, the chemical positive drug control group, and the marketed traditional Chinese medicine control group in improving atrial premature beats, ventricular premature beats, and regulating sinus tachycardia. It also has the dual advantages of rapid onset of action and long duration of efficacy, and has the comprehensive characteristics of rapid symptom intervention and long-term homeostasis regulation. The differences between the groups are statistically significant (P<0.05).

[0042] Test group Myocardial MDA (nmol / mg prot) Myocardial SOD (U / mg prot) Myocardial TNF-α (pg / ml) Model control group 6.82±0.53 86.35±6.42 124.56±10.32 Chemical positive control group 5.96±0.47 92.45±6.85 112.35±9.26 Control group of marketed traditional Chinese medicines 5.52±0.44 101.36±7.12 99.68±8.35 First active monomer single-use group 5.28±0.42 109.54±7.32 93.46±7.52 Second active monomer single-use group 5.01±0.40 115.68±7.56 87.53±7.18 The compound of the present invention 3.91±0.29 135,28±8.15 68.49±5.36 Experimental data confirm that the compound formulation system of this invention can significantly reduce the level of oxidative stress damage in myocardial tissue, inhibit the inflammatory pathological process of myocardium, and its overall myocardial protective effect is superior to that of single active monomers and existing Chinese and Western medicine control preparations. The differences between groups are statistically significant (P<0.05). It can simultaneously achieve the dual therapeutic value of arrhythmia rhythm intervention and myocardial pathological damage repair.

[0043] V. Indications It is used to improve atrial premature beats, ventricular premature beats, and sinus tachycardia.

[0044] VI. Applicable Groups This preparation is suitable for patients with functional and mild pathological atrial premature beats, ventricular premature beats, and sinus tachycardia; it is not suitable for patients with severe organic heart disease, malignant arrhythmias, or heart failure.

[0045] VII. Beneficial Effects of the Invention 1. This invention adopts a dual-layer composite controlled-release structure design that combines rapid-release and sustained-release properties, while also taking into account both rapid symptom intervention and long-term steady-state rhythm regulation. This effectively solves the shortcomings of traditional Chinese medicine preparations, such as slow onset of action, large fluctuations in blood drug concentration, and unstable rhythm control in ordinary fast-release preparations.

[0046] 2. The two natural active monomers of this invention form a scientifically combined system with a clear division of primary and secondary functions and complementary secondary pharmacological effects. This system can not only target and regulate abnormal electrical activity of the myocardium and rapidly improve symptoms of arrhythmia, but also comprehensively protect myocardial cells, optimize the myocardial circulatory microenvironment, and repair intrinsic pathological damage to the myocardium. This comprehensive treatment approach aligns with the treatment concept of addressing both the symptoms and the root cause.

[0047] 3. This invention fully utilizes the dose-dependent pharmacological characteristics and mutual balancing compatibility of active monomers, resulting in a mild and stable overall drug effect. It effectively avoids high-risk adverse reactions such as conduction abnormalities and myocardial depression that are easily caused by chemical antiarrhythmic drugs, and has higher safety for long-term continuous use.

[0048] 4. The formulation of this invention is concise and scientific, the raw and auxiliary materials are widely available, the overall preparation process is mature and controllable, the product quality has good repeatability, it is easy to implement on a large scale and industrial basis, and it has good clinical promotion value and industrial application prospects. Detailed Implementation

[0049] The technical solution of the present invention will be described in detail below with reference to specific embodiments. The following embodiments are only used to explain the present invention and are not intended to limit the scope of protection of the present invention.

[0050] Example: Preparation of compound antiarrhythmic bilayer sustained-release formulation Composition of a single-dose finished product prescription: Immediate-release layer: First active monomer 22mg, second active monomer 20mg, lactose 45mg, microcrystalline cellulose 30mg, crospovidone 8mg, hydroxypropyl methylcellulose 3mg, magnesium stearate 1.5mg; Sustained-release layer: 8mg of first active monomer, 15mg of second active monomer, 25mg of hydroxypropyl methylcellulose, 40mg of lactose, 25mg of microcrystalline cellulose, 2.5mg of povidone, and 1.5mg of magnesium stearate.

[0051] Preparation steps: 1. Pass each active monomer and pharmaceutical excipient in the prescription through a standard sieve (100 mesh) according to the Chinese Pharmacopoeia, and set aside for later use; 2. Prepare immediate-release layer particles and sustained-release layer particles respectively according to the aforementioned preparation process requirements of this invention; 3. Using a double-layer tablet press, the filler is layered and the appropriate tableting pressure is adjusted to compress the tablets into double-layer tablets, thus obtaining the compound antiarrhythmic double-layer sustained-release formulation of the present invention.

Claims

1. A compound bilayer sustained-release formulation for treating arrhythmia, characterized in that: The formulation is a bilayer sustained-release tablet structure, consisting of an immediate-release layer and a sustained-release layer pressed together; the formulation contains two natural plant-purified functional monomers as core active ingredients, and each active monomer is distributed in the immediate-release layer and the sustained-release layer according to a defined dosage; the formulation is used to improve atrial premature beats, ventricular premature beats, and sinus tachycardia.

2. The antiarrhythmic compound bilayer sustained-release formulation according to claim 1, characterized in that: One of the active monomers has the core function of regulating myocardial electrophysiology and antagonizing arrhythmia, while also having auxiliary activities such as dilating coronary arteries, improving myocardial microcirculation, and protecting cardiomyocytes. Moreover, the pharmacological effects of this monomer are dose-dependent. Another active monomer has the core functions of stabilizing myocardial cell membranes, improving myocardial microcirculation, and repairing myocardial micro-damage, while also having the activity of assisting in stabilizing myocardial electrophysiology; the two monomers have a clear division of primary and secondary functions, and their secondary pharmacological effects are superimposed and synergistic.

3. The antiarrhythmic compound bilayer sustained-release formulation according to claim 1, characterized in that: This preparation is suitable for people with functional and mild pathological arrhythmias; it is not suitable for patients with severe organic heart disease, malignant arrhythmias, or heart failure.

4. The antiarrhythmic compound bilayer sustained-release formulation according to claim 1, characterized in that: The sustained-release layer is prepared using a hydrophilic framework constant-temperature dissolution and release process. The immediate-release layer and the sustained-release layer are layered and pressed together without cross-mixing. All raw and auxiliary materials meet the pharmacopoeia standards.