Pharmaceutical composition for treating arrhythmia and application thereof

Abstract

The invention relates to the technical field of biological medicines, in particular to a pharmaceutical composition for treating arrhythmia and application thereof. The invention provides a pharmaceutical composition for treating arrhythmia. The pharmaceutical composition comprises levistilide A, spinosin and L-tetrahydropalmatine. Through the synergistic effect of the levistilide A, spinosin and L-tetrahydropalmatine, the composition disclosed by the invention can be used for effectively treating arrhythmia, especially tachyarrhythmia. Experimental data show that in a mouse ventricular fibrillation model induced by chloroform and a rat ventricular arrhythmia model induced by barium chloride, the composition remarkably reduces the occurrence rate of ventricular fibrillation and shortens the sinus rhythm recovery time, and the effect of the composition is equivalent to or even better than that of a positive control drug. The obvious curative effect of the composition in the anti-arrhythmia aspect is fully proved.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a pharmaceutical composition for treating arrhythmia and application thereof. Background Art

[0002] Arrhythmias are common cardiovascular diseases caused by abnormalities in the cardiac electrical conduction system. Clinical manifestations include palpitations, dizziness, syncope, and even sudden death. Currently, the treatment of arrhythmias relies primarily on antiarrhythmic drugs (AADs), such as sodium channel blockers (e.g., quinidine), beta-blockers (e.g., metoprolol), and potassium channel blockers (e.g., amiodarone). However, existing drugs generally suffer from limited efficacy, significant side effects (e.g., risk of arrhythmias and organ toxicity), and poor patient tolerance. There is an urgent need to develop safer and more effective drug combination regimens.

[0003] In recent years, combination drug therapy has become an important strategy for arrhythmia management, enhancing efficacy and reducing the dose-dependent side effects of single-drug therapies through multi-target synergy. For example, the combination of amiodarone and beta-blockers can reduce the recurrence of ventricular arrhythmias, but long-term use may still lead to thyroid dysfunction or pulmonary fibrosis. Furthermore, some newer ion channel modulators (such as ibutilide), while effective for atrial fibrillation, carry the risk of inducing torsades de pointes. Therefore, optimizing drug combinations to balance efficacy and safety has become a key research focus.

[0004] With the deepening of research on the mechanism of arrhythmia, it has been found that pathological processes such as inflammation, oxidative stress and calcium regulation imbalance are also involved in the progression of the disease, which provides new ideas for the design of drug combinations targeting multiple pathways. For example, drugs with both anti-inflammatory and ion channel regulating effects may enhance the anti-arrhythmic effect through synergistic mechanisms. However, existing compositions are mostly limited to the simple superposition of traditional antiarrhythmic drugs and lack precise compatibility for multiple pathological links. Therefore, the development of a composite drug composition based on multi-mechanism synergy and controllable side effects is of great clinical significance. Summary of the Invention

[0005] The purpose of the present invention is to provide a pharmaceutical composition for treating arrhythmia and its application.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions: The present invention provides a pharmaceutical composition for treating arrhythmia, comprising angelica lactone A, spinosadone and levorotatory tetrahydropalmatine.

[0007] Preferably, the mass ratio of angelica lactone A, spinosin and levorotatory tetrahydropalmatine is 20-30:7-13:12-16.

[0008] Preferably, the arrhythmia is a tachyarrhythmia.

[0009] The present invention also provides the use of the pharmaceutical composition for treating arrhythmia in preparing a drug for treating arrhythmia.

[0010] The present invention also provides a medicine for treating arrhythmia, comprising the pharmaceutical composition for treating arrhythmia and auxiliary materials.

[0011] Preferably, the dosage form of the drug is tablet, injection, capsule, granule or aerosol.

[0012] Compared with the prior art, the present invention has the following beneficial effects: The pharmaceutical composition provided by the present invention has significant beneficial technical effects. The synergistic effects of eugenolide A, spinosin, and levorotatory tetrahydropalmatine are primarily achieved through multi-target regulation of cardiac electrophysiological function: eugenolide A inhibits abnormal calcium influx into myocardial cells and stabilizes action potential duration; spinosin has antioxidant and anti-inflammatory effects, alleviating myocardial oxidative stress damage while regulating potassium channels and improving repolarization; and levorotatory tetrahydropalmatine inhibits abnormal excitation conduction by blocking sodium channels. Together, these three enhance the regulation of cardiac ion channels (sodium, potassium, and calcium), inhibiting triggered activity and reentry mechanisms, thereby effectively correcting tachyarrhythmias and reducing the risk of ventricular fibrillation.

[0013] The composition of the present invention, through the synergistic effects of eugenolide A, spinosin, and levorotatory tetrahydropalmatine, can effectively treat arrhythmias, particularly tachyarrhythmias. Experimental data showed that the composition significantly reduced the incidence of ventricular fibrillation and shortened the time to sinus rhythm recovery in both chloroform-induced mouse models of ventricular fibrillation and barium chloride-induced rat models of ventricular arrhythmia, achieving results comparable to or even superior to those of the positive control drug. This fully demonstrates the composition's significant anti-arrhythmic efficacy.

[0014] Secondly, through its multi-target mechanism of action, this pharmaceutical composition not only regulates the cardiac electrical conduction system but also potentially mitigates myocardial damage through anti-inflammatory and antioxidant pathways, thereby treating arrhythmias while reducing side effects. Compared to existing single-ingredient drugs or simple combination drugs, the composition provided by the present invention has higher safety and tolerability. Experimental results show that the components of the composition exhibit optimal synergistic effects within a specific mass ratio range (the mass ratio of angelica lactone A, spinosin, and levorotatory tetrahydropalmatine is 20-30:7-13:12-16), further optimizing the therapeutic effect.

[0015] Finally, the pharmaceutical composition of the present invention has diverse dosage forms and can be prepared into various forms such as tablets, injections, capsules, granules, or aerosols according to clinical needs, thereby improving the applicability of the drug and patient compliance. In addition, the raw materials of the composition are widely available, the preparation process is relatively simple, and it has good prospects for industrial production. In summary, the present invention not only fills the deficiencies of existing antiarrhythmic drugs in terms of efficacy and safety, but also provides a new option for the clinical treatment of arrhythmias, and has important clinical application value. DETAILED DESCRIPTION

[0016] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0017] Example 1 A pharmaceutical composition for treating tachyarrhythmia, comprising eugenolide A, spinosin, and levorotatory tetrahydropalmatine in a mass ratio of 22:8:13.

[0018] Example 2 A pharmaceutical composition for treating tachyarrhythmia, comprising eugenolide A, spinosin, and levorotatory tetrahydropalmatine in a mass ratio of 24:9:14.

[0019] Example 3 A pharmaceutical composition for treating tachyarrhythmia, comprising eugenolide A, spinosin, and levorotatory tetrahydropalmatine in a mass ratio of 20:7:12.

[0020] Example 4 A pharmaceutical composition for treating tachyarrhythmia, comprising eugenolide A, spinosin, and levorotatory tetrahydropalmatine in a mass ratio of 30:13:16.

[0021] Example 5 A pharmaceutical composition for treating tachyarrhythmia, comprising eugenolide A, spinosin, and levorotatory tetrahydropalmatine in a mass ratio of 25:10:14.

[0022] Example 6 A pharmaceutical composition for treating tachyarrhythmia, comprising angelica lactone A and spinosin in a mass ratio of 25:10.

[0023] Example 7 A pharmaceutical composition for treating tachyarrhythmia, comprising spinosin and levorotatory tetrahydropalmatine in a mass ratio of 10:14.

[0024] Example 8 A pharmaceutical composition for treating tachyarrhythmia, consisting of angelica lactone A.

[0025] Experimental Example 1 Experimental animals: Kunming mice (clean grade), weighing 20±2 g, half male and half female, were purchased from Liaoning Changsheng Biotechnology.

[0026] Experimental methods and results (1) Chloroform-induced ventricular fibrillation in mice Animal Grouping: Sixty healthy Kunming mice were selected and randomly divided into 6 groups (n=10, half male and half female): 1) Model group; 2) positive control group (diltiazem, 4 mg / kg); 3) Experimental group (the pharmaceutical composition obtained in Example 5 was dissolved and then administered by injection, with an actual dosage of 15 mg / kg); Examples 6 to 8 were used as control groups 1 to 3, respectively, and their usage was the same as that of the experimental group.

[0027] (2) Medication treatment: Each group received the corresponding drug via the tail vein, while the model group received an equal volume of normal saline. Two minutes after drug administration, the mice were placed in a container containing a chloroform cotton ball. After the mice stopped breathing, the chest cavity was quickly opened, the heart exposed, and ventricular fibrillation was observed visually. The results were recorded and statistically analyzed (Table 1).

[0028] Table 1 Survey results

[0029] As shown in Table 1, the incidence of ventricular fibrillation (30%) in the experimental group (three-component combination) of the present invention was significantly lower than that in the model group (100%) and close to that of the positive control drug diltiazem (20%), demonstrating that the composition has a significant anti-ventricular fibrillation effect. Notably, the incidence of ventricular fibrillation in each control group (single and double component combinations) (50%-70%) was higher than that in the experimental group, suggesting a synergistic effect of the three-component combination. Control group 3, containing only angelica lactone A, had the lowest efficacy (70%), demonstrating that the effects of individual components are limited and require specific combinations in specific proportions for optimal efficacy.

[0030] Experimental Example 2 Experimental method of ventricular arrhythmia induced by barium chloride in rats: Experimental animals and groups: SD rats (clean grade), weighing 130 ± 10 g, were purchased from Liaoning Changsheng Biotechnology.

[0031] Sixty healthy SD rats, half male and half female, were randomly divided into 6 groups (n=10, half male and half female): 1) Normal saline group (negative control group) 2) Lidocaine group (5 mg / kg) 3) Experimental group (the pharmaceutical composition obtained in Example 5 was dissolved and then administered by injection, with an actual dosage of 15 mg / kg); Examples 6 to 8 were used as control groups 1 to 3, respectively, and their usage was the same as that of the experimental group.

[0032] (1) Experimental operation process: Anesthesia: Intraperitoneal injection of 10% chloral hydrate solution (300 mg / kg) for anesthesia Fixation and monitoring: After dorsal fixation, connect to the physiological signal acquisition system Basic recording: Collect and record normal electrocardiogram of lead II Modeling: Arrhythmia was induced by injecting barium chloride solution (4 mg / kg) into the lingual vein. After the arrhythmia stabilized for 3 minutes, each group was given the corresponding drugs: Observation indicators: Recovery of sinus rhythm Time required to restore sinus rhythm (average) Number of animals whose sinus rhythm was restored and maintained for ≥5 min Number of animals whose sinus rhythm was restored and maintained for ≥20 min The experimental results are shown in Table 2.

[0033] Table 2 Experimental results

[0034] As shown in Table 2, the experimental group significantly outperformed the model group in terms of sinus rhythm recovery time (57.4 seconds), recovery rate (70%), and rhythm maintenance time (≥5 minutes, 30%). Some indicators approached those of the lidocaine positive control. Compared with the control group, the experimental group experienced a shorter recovery time (116.4-165.7 seconds for controls 1-3) and better maintenance stability, further validating the rapid onset and sustained action of the three-component combination. These results not only confirm the efficacy of the combination against tachyarrhythmias but also suggest that it may achieve broad-spectrum antiarrhythmic effects through multiple target mechanisms, such as ion channel regulation and antioxidant activity.

[0035] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for treating arrhythmia, characterized in that: Including angelica lactone A, spinosadine and levorotatory tetrahydropalmatine.

2. A pharmaceutical composition for treating arrhythmia according to claim 1, characterized in that: The mass ratio of the angelica lactone A, spinosin and levorotatory tetrahydropalmatine is 20-30:7-13:12-16.

3. The pharmaceutical composition for treating arrhythmia according to claim 1, characterized in that: The arrhythmia is a tachyarrhythmia.

4. Use of the pharmaceutical composition for treating arrhythmia according to any one of claims 1 to 3 in the preparation of a medicament for treating arrhythmia.

5. A drug for treating arrhythmia, characterized in that: The invention comprises the pharmaceutical composition for treating arrhythmia according to any one of claims 1 to 3 and excipients.

6. The drug for treating arrhythmia according to claim 5, characterized in that: The dosage form of the medicine is tablet, injection, capsule, granule or aerosol.

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