Application of traditional Chinese medicine composition in medicine for preventing and treating ventricular arrhythmia

Abstract

The invention discloses an application of a traditional Chinese medicine composition in a medicine for preventing and treating ventricular arrhythmia. The traditional Chinese medicine composition comprises ginseng, lucid ganoderma, safflower, musk, calculus bovis, bear gall, pearl, venenum bufonis, radix aconiti carmichaeli and borneol. Wherein the mass ratio of the ginseng, the pearl and the lucid ganoderma is 11%-70% respectively and independently. According to the traditional Chinese medicine composition disclosed by the invention, through reasonable compatibility of all the components, the symptoms of ventricular arrhythmia can be effectively relieved from multiple aspects through at least one of ventricular premature beat, ventricular tachycardia, ventricular fibrillation occurrence time, QTc, PR interval and QRS wave group time which are improved through sleep regulation, and the progress of a disease course is blocked. The traditional Chinese medicine composition is controllable in quality, convenient for standardized production, safe and reliable in prescription and free of toxic and side effects on human bodies.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to application of a traditional Chinese medicine composition in medicine for preventing and treating ventricular arrhythmia. Background Art

[0002] Ventricular arrhythmias are very common arrhythmias in clinical practice, mainly including premature ventricular beats (PVT), ventricular tachycardia (VT), ventricular flutter (VF) and ventricular fibrillation (VF). Ventricular arrhythmias often occur in patients with structural heart disease and ion channel disease, but they are also not uncommon in people with normal heart structure. Clinically, the manifestations of patients vary greatly. Some may be asymptomatic, while others have clear palpitations, chest tightness or blackouts. In severe cases, they may even lead to sudden cardiac death (SCD). The mechanism of ventricular arrhythmias is abnormal increase in automaticity, triggered activity caused by early and late afterdepolarizations, and reentry. Epidemiological data show that the incidence of premature ventricular beats in the general population is 1% to 4%, and the prevalence of premature ventricular beats found in surface electrocardiogram screening is about 1%, and the prevalence of premature ventricular beats found in 24h or 48h dynamic electrocardiogram testing can be as high as 40% to 75%. The 24h dynamic electrocardiogram monitoring of asymptomatic healthy people found that the rate of non-sustained ventricular tachycardia was 0 to 3%. Nearly 90% of sustained monomorphic ventricular tachycardia occurs in patients with structural heart disease such as coronary heart disease, while only 10% of patients do not have structural heart disease. Sustained polymorphic ventricular tachycardia and ventricular fibrillation are usually seen in patients with inherited arrhythmia syndromes, but there are no exact statistics. The incidence of ventricular fibrillation in patients with acute myocardial infarction is about 15%, of which 80% occur within 6 hours after myocardial infarction; if ventricular fibrillation occurs in chronic myocardial ischemia, the recurrence rate in 1 year is >30%. Rapid ventricular rate and polymorphic ventricular tachycardia, ventricular flutter and ventricular fibrillation are the main causes of SCD.

[0003] Ventricular arrhythmia is a common type of arrhythmia in clinical practice. It belongs to the category of "palpitations" and "flustered palpitations" in traditional Chinese medicine. Symptoms such as palpitations, dizziness, and fatigue are common during attacks. Due to the accelerated pace of modern life and the increased intensity of mental work, mental-related diseases are becoming more and more common, such as sleep disorders, anxiety, and depression. Emotional disorders, excessive worry, tediousness, and lack of inner mind; phlegm and dampness, blood stasis, such as atherosclerosis, block the blood vessels, and the mind loses its nourishment, or real evil directly disturbs the mind, which can all cause anxiety, insomnia, and mental lesions. Mental diseases lead to abnormal control and regulation functions, and heart rhythm and frequency disorders, resulting in palpitations (ventricular arrhythmia). The disordered heartbeat, pulse disorder, and abnormal blood circulation during ventricular arrhythmia attacks will lead to the endogenous generation of phlegm and blood stasis, poor blood circulation, and lack of nourishment for the mind, thereby aggravating the pulse and mental lesions and forming a vicious circle.

[0004] Modern medicine holds that conditions or diseases such as excessive work pressure or coronary atherosclerotic heart disease can all affect mental state, and abnormal mental state can trigger ventricular arrhythmia by affecting the function of the autonomic nervous system and activating the hypothalamic-pituitary-adrenal-angiotensin-aldosterone system. Abnormal autonomic regulation involves ion channel abnormalities, inflammatory responses, oxidative stress, etc., as well as atrial structural remodeling and electrical remodeling caused by these pathological changes, which are important mechanisms for the occurrence and maintenance of ventricular arrhythmia. At the same time, ventricular arrhythmia can also cause the above-mentioned pathological changes, leading to cardiac structural remodeling and electrical remodeling, forming a vulnerable basis for the onset of ventricular arrhythmia, increasing the susceptibility to ventricular arrhythmia, and maintaining ventricular arrhythmia; further aggravating the symptoms of diseases such as depression, anxiety or coronary heart disease.

[0005] In view of the above pathogenesis or molecular mechanism, calming the mind, tonifying qi and nourishing the heart, and regulating the mind are one of the important strategies for traditional Chinese medicine to treat arrhythmia; that is, improving myocardial energy metabolism and achieving the therapeutic effect of the disease by improving the patient's sleep and emotional regulation function. Summary of the Invention

[0006] The present invention aims to at least solve one of the above technical problems existing in the prior art. For this purpose, the object of the present invention is to provide an application of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating ventricular arrhythmia.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] The present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating ventricular arrhythmia, wherein the traditional Chinese medicine composition includes ginseng, ganoderma lucidum, safflower, musk, bezoar, bear bile, pearl, bufotoxin, aconite root and borneol; wherein, the mass ratios of ginseng, pearl and ganoderma lucidum are independently 11% - 70%.

[0009] The related technology CN108057066A discloses a pharmaceutical composition for preventing and treating unstable angina pectoris, which is composed of ginseng, aconite, ganoderma lucidum, safflower, artificial musk, bear bile, pearl, bufotoxin, borneol and bezoar. The inventor surprisingly found that by greatly adjusting the compatibility ratio of this formula, especially increasing the mass ratio of ginseng, pearl and ganoderma lucidum, its original characteristics of mainly promoting qi and activating blood circulation, warming meridians and dredging collaterals are transformed into mainly promoting qi and nourishing the heart, calming the mind and stabilizing the will. The traditional Chinese medicine composition with the new compatibility composition ratio shows good therapeutic effects on ventricular arrhythmia. A large amount of experimental data prove that through the reasonable compatibility of each component, the new composition can effectively improve the occurrence time of ventricular premature beats (VP), ventricular tachycardia (VT), and ventricular fibrillation (VF) of ventricular arrhythmia by improving sleep, relieve the symptoms of ventricular arrhythmia from multiple aspects, and block the progression of the disease process. The prescription is safe and reliable, and has no toxic and side effects on the human body. In the formula, safflower and ginseng help ganoderma lucidum to promote qi and nourish the heart, greatly tonify primordial qi, restore pulse and arrest sweating, tonify the heart and nourish blood, so as to make qi abundant and blood smooth. The exertion of the calming and convulsion-arresting effect of pearl is combined with ganoderma lucidum, which is used in combination with mutual reinforcement, synergistically enhancing the effect, and broadening the scope of calming and convulsion-arresting of pearl; pearl is combined with the qi-tonifying drug ginseng to improve restlessness and insomnia; it is combined with phlegm-resolving drugs such as bezoar to clear heat and resolve phlegm, and extinguish wind and stop convulsions. Musk and bufotoxin are pungent, dispersing, warm and dredging, fragrant and spreading, opening orifices and relieving arthralgia, dredging meridians and relieving pain; aconite is pungent, warm and dry, tonifying fire and assisting yang, dispersing cold and relieving arthralgia, which can not only help ganoderma lucidum to promote qi and activate yang, but also prevent the cold nature of bezoar, bear bile and pearl. Bezoar, bufotoxin, bear bile and borneol are adjuvant drugs, and the four drugs together play the effects of opening orifices and clearing the heart, relieving pain and arresting convulsions. Understood by modern pharmacology, traditional Chinese medicine clinical applications and preclinical studies show that ganoderma lucidum has the effects of promoting qi and calming the mind and anti-arrhythmia, pearl has the effects of calming the mind, anti-convulsion and anti-arrhythmia, low-dose aconite (aconitine) has the effects of sedation and promoting sleep, and bezoar, bear bile and borneol have the effects of relieving pain and arresting convulsions.

[0010] In some embodiments of the present invention, the mass ratios of the ginseng, pearl and ganoderma lucidum are each independently 11% - 70%, such as 13% - 70%, 15% - 61%, 15 - 63%, 11% - 46%, 11 - 41%, 22% - 70%.

[0011] In some embodiments of the present invention, the mass ratios of the ginseng, pearl and ganoderma lucidum are 11% - 46%, 11 - 41%, 22% - 70% respectively.

[0012] In some embodiments of the present invention, by mass, the traditional Chinese medicine composition includes 700 - 1500 parts of ginseng, 10 - 50 parts of musk, 5 - 50 parts of bezoar, 5 - 50 parts of bear bile, 20 - 60 parts of bufotoxin, 700 - 1500 parts of pearl, 5 - 20 parts of borneol, 700 - 1500 parts of ganoderma lucidum, 50 - 120 parts of safflower, and 5 - 15 parts of aconite.

[0013] In some embodiments of the present invention, based on parts by mass, the traditional Chinese medicine composition comprises 750 - 1500 parts of ginseng, 15 - 50 parts of moschus, 10 - 50 parts of calculus bovis, 8 - 50 parts of fel ursi, 25 - 60 parts of bufonis venom, 750 - 1450 parts of margarita, 8 - 20 parts of borneol, 750 - 1450 parts of ganoderma lucidum, 60 - 110 parts of carthamus tinctorius, and 7 - 15 parts of aconite lateralis preparata.

[0014] In some embodiments of the present invention, based on parts by mass, the traditional Chinese medicine composition comprises 200 - 400 parts of ginseng, 10 - 60 parts of moschus, 5 - 50 parts of calculus bovis, 5 - 50 parts of fel ursi, 20 - 60 parts of bufonis venom, 200 - 350 parts of margarita, 5 - 20 parts of borneol, 400 - 600 parts of ganoderma lucidum, 5 - 20 parts of aconite lateralis preparata, and 20 - 150 parts of carthamus tinctorius.

[0015] In some embodiments of the present invention, the calculus bovis includes in vitro cultivated calculus bovis.

[0016] In some embodiments of the present invention, the moschus includes artificial moschus.

[0017] In some embodiments of the present invention, the prevention and treatment of ventricular arrhythmia includes preventing and / or treating ventricular arrhythmia; the prevention and treatment of ventricular arrhythmia includes improving ventricular arrhythmia; the prevention and treatment of ventricular arrhythmia includes improving at least one of the occurrence times of ventricular premature beats (VP), ventricular tachycardia (VT), and ventricular fibrillation (VF).

[0018] In some embodiments of the present invention, the improvement of ventricular arrhythmia includes the improvement of at least one efficacy index such as QTc, PR interval, and QRS complex duration.

[0019] In some embodiments of the present invention, the prevention and treatment of ventricular arrhythmia includes preventing and / or treating ventricular arrhythmia by improving sleep.

[0020] In some embodiments of the present invention, the improvement of sleep includes the improvement of at least one efficacy index such as sleep latency, sleep duration, Glu, GABA, and Glu / GABA levels in the brain tissue.

[0021] In some embodiments of the present invention, the traditional Chinese medicine composition further comprises pharmaceutically acceptable excipients.

[0022] In some embodiments of the present invention, the pharmaceutically acceptable excipients include at least one of fillers, disintegrants, diluents, lubricants, binders, wetting agents, flavoring agents, suspending agents, solvents, sustained-release agents, emulsifiers, vegetable oils, absorption promoters, surfactants, or preservatives.

[0023] In some embodiments of the present invention, the filler is selected from starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, glucose, etc.; the binder is selected from cellulose derivatives, alginates, starch, water, dextrin, gelatin, hydroxypropyl cellulose, methyl cellulose, polyvinylpyrrolidone, etc.; the diluent is selected from at least one of lactose, sucrose, mannitol, corn starch, potato starch, calcium phosphate, calcium citrate, and crystalline cellulose; the disintegrant is selected from at least one of corn starch, potato starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, carboxymethyl cellulose, cross-linked carboxymethyl cellulose sodium, calcium carboxymethyl cellulose, and alginic acid; the lubricant is selected from at least one of stearic acid, polyethylene glycol, calcium carbonate, sodium bicarbonate, colloidal silicon dioxide, talc, anhydrous silica gel, and magnesium stearate; the suspending agent is selected from at least one of colloidal silicon dioxide, beeswax, cellulose, sodium carboxymethyl cellulose, and solid polyethylene glycol; the wetting agent is selected from at least one of glycerol, Tween-80, oxyhydrogenated castor oil, sodium lauryl sulfate, and lecithin; the solvent is selected from at least one of water, ethanol, liquid polyethylene glycol, isopropanol, Tween-80, glycerol, propylene glycol, and vegetable oil, and the vegetable oil is selected from rapeseed oil, beeswax, soybean oil, castor oil, peanut oil, blended oil, etc.; the surfactant is selected from at least one of sodium dodecylbenzenesulfonate, stearic acid, polyoxyethylene-polyoxypropylene copolymer, sorbitan fatty acid ester, and polysorbate (Tween); the flavoring agent is selected from at least one of aspartame, sucralose, essence, steviol glycoside, acesulfame potassium, citric acid, and sodium saccharin; the preservative is selected from at least one of methyl p-hydroxybenzoate or propyl p-hydroxybenzoate.

[0024] In some embodiments of the present invention, the traditional Chinese medicine composition can be prepared by conventional methods in the art. The traditional Chinese medicine composition of the present invention is a composition formed by mixing the raw materials of each component after pulverization; and / or an extract obtained by extracting the raw materials of each component after mixing; and / or an extract obtained by separately extracting the raw materials of each component and then mixing. Optionally, the extract is further refined and purified. Among them, the extraction methods include decoction extraction, reflux extraction, maceration extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc.; the purification methods include water extraction and alcohol precipitation, alkali solution and acid precipitation, and / or various column chromatography purification methods, such as macroporous resin column, silica gel column, gel column, reverse phase column, etc.

[0025] In some embodiments of the present invention, the dosage form of the traditional Chinese medicine composition includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder, or ointment.

[0026] In some embodiments of the present invention, the traditional Chinese medicine composition is made into any one of the corresponding decoction, tablet, capsule, granule, pill, oral liquid, powder, or ointment according to the conventional preparation process of the required dosage form.

[0027] In some embodiments of the present invention, when the traditional Chinese medicine composition is in the form of pills, the preparation method of the traditional Chinese medicine composition comprises the following steps:

[0028] Sprinkle and mix the powders of each component of the raw materials of traditional Chinese medicine, and spray water to obtain the pills of the traditional Chinese medicine composition.

[0029] In some embodiments of the present invention, the preparation method of the traditional Chinese medicine composition comprises the following steps: sprinkle and mix the powders of each component of the raw materials of traditional Chinese medicine in batches, and spray water to obtain the pills of the traditional Chinese medicine composition.

[0030] The beneficial effects of the present invention are as follows:

[0031] Through the reasonable compatibility of each component, the traditional Chinese medicine composition of the present invention can effectively improve at least one of the appearance time of ventricular premature beats (VP), ventricular tachycardia (VT), ventricular fibrillation (VF), QTc, PR interval, and QRS complex time through sleep regulation, relieve the symptoms of ventricular arrhythmia from multiple aspects, and block the progression of the disease course. The traditional Chinese medicine composition of the present invention has controllable quality, is convenient for standardized production, has a safe and reliable prescription, and has no toxic and side effects on the human body. Description of the Drawings

[0032] Figure 1 It shows the effects of drug administration in each group on the sleep latency of mice in the test examples of the present invention.

[0033] Figure 2 It shows the effects of drug administration in each group on the sleep duration of mice in the test examples of the present invention.

[0034] Figure 3 It shows the effects of drug administration in each group on the body weight of mice in the test examples of the present invention. Detailed Embodiments

[0035] The content of the present invention will be further described in detail through specific examples below. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial channels or can be obtained by existing technical methods. Unless otherwise specified, the test or measurement methods are all conventional methods in the art.

[0036] Example 1

[0037] In this example, a traditional Chinese medicine composition was prepared, and the specific process was as follows:

[0038] Calculated by parts by mass, the composition of the traditional Chinese medicine composition is: 750 parts of ginseng, 15 parts of musk, 10 parts of bezoar, 8 parts of bear bile, 25 parts of bufotalin, 750 parts of pearl, 8 parts of borneol, 750 parts of ganoderma lucidum, 60 parts of safflower, and 7 parts of aconite.

[0039] The preparation method is as follows: all medicinal materials are separately powdered and then mixed; a built-in water spraying device is installed in the coating pan. The medicinal powder is scattered into the coating pan. First, a small amount of medicinal powder is added, the water spraying is started for 2 minutes and the coating pan is rotated; the water spraying is stopped, and the coating pan is continuously rotated. The water spraying and powder scattering are repeated until the particles are firm, forming firm and dense particles. Subsequently, screening is carried out using a pill mold with a 1 mm aperture, and the pills with a diameter of 1 mm are collected, which are the finished products.

[0040] Example 2

[0041] In this example, a traditional Chinese medicine composition was prepared. The specific process was as follows:

[0042] Calculated by mass parts, the composition of the traditional Chinese medicine composition is: 1250 parts of ginseng, 32 parts of musk, 30 parts of bezoar, 29 parts of bear bile, 43 parts of bufotoxin, 1100 parts of pearl, 14 parts of borneol, 1100 parts of ganoderma lucidum, 85 parts of safflower, and 11 parts of aconite root.

[0043] Its preparation method refers to Example 1.

[0044] Example 3

[0045] In this example, a traditional Chinese medicine composition was prepared. The specific process was as follows:

[0046] Calculated by mass parts, the composition of the traditional Chinese medicine composition is: 1500 parts of ginseng, 50 parts of musk, 50 parts of bezoar, 50 parts of bear bile, 60 parts of bufotoxin, 1450 parts of pearl, 20 parts of borneol, 1450 parts of ganoderma lucidum, 110 parts of safflower, and 15 parts of aconite root.

[0047] Its preparation method refers to Example 1.

[0048] Comparative Example 1

[0049] In this comparative example, a traditional Chinese medicine composition was prepared. The specific process was as follows:

[0050] Calculated by mass parts, the composition of the traditional Chinese medicine composition is: 100 parts of ginseng, 32 parts of musk, 30 parts of bezoar, 29 parts of bear bile, 43 parts of bufotoxin, 1100 parts of pearl, 14 parts of borneol, 100 parts of ganoderma lucidum, 85 parts of safflower, and 11 parts of aconite root.

[0051] Its preparation method refers to Example 1.

[0052] Comparative Example 2

[0053] In this comparative example, a traditional Chinese medicine composition was prepared. The specific process was as follows:

[0054] Calculated by mass parts, the composition of the traditional Chinese medicine composition is: 1250 parts of ginseng, 32 parts of musk, 30 parts of bezoar, 29 parts of bear bile, 43 parts of bufotoxin, 100 parts of pearl, 14 parts of borneol, 1100 parts of ganoderma lucidum, 85 parts of safflower, and 11 parts of aconite root.

[0055] The preparation method refers to Example 1.

[0056] Comparative Example 3

[0057] A traditional Chinese medicine composition was prepared in this comparative example. The specific process was as follows:

[0058] Based on parts by mass, the composition of the traditional Chinese medicine composition was: 100 parts of ginseng, 32 parts of moschus, 30 parts of calculus bovis, 29 parts of fel ursi, 43 parts of bufonis, 100 parts of margarita, 14 parts of borneol, 100 parts of ganoderma lucidum, 85 parts of flos carthami, and 11 parts of aconite lateralis preparata.

[0059] The preparation method refers to Example 1.

[0060] Comparative Example 4

[0061] A traditional Chinese medicine composition was prepared in this comparative example. The specific process was as follows:

[0062] Based on parts by mass, the composition of the traditional Chinese medicine composition was: 156 parts of ginseng, 35 parts of aconite lateralis preparata, 175 parts of ganoderma lucidum, 266 parts of flos carthami, 30 parts of artificial moschus, 50 parts of fel ursi, 65 parts of margarita, 75 parts of bufonis, 30 parts of borneol, and 70 parts of calculus bovis.

[0063] The preparation method refers to Example 1.

[0064] Test Example

[0065] 1 Experimental method

[0066] 1.1 Model establishment

[0067] Preparation of ventricular arrhythmia model: A ventricular arrhythmia model was prepared by subcutaneous injection of 5 mg / kg ISO (isoproterenol) for 6 consecutive days, and then intraperitoneal injection of 3 mg / kg ISO for 1 consecutive day. Electrocardiogram was monitored for 1 h. The appearance of enlarged and deformed QRS complexes in the electrocardiogram indicated successful model establishment.

[0068] Preparation of insomnia model: Starting from the first day after successful establishment of the ventricular arrhythmia model, except for the control group, the remaining mice were intraperitoneally injected with a suspension of parachlorophenylalanine (PCPA) (0.04 g·mL -1 ) for three consecutive days to induce an insomnia model. Taking the time of the first intraperitoneal injection as the starting point, each mouse was independently placed in a cage for 5 min after 28 - 36 h, and then the behavioral performance of the mouse was observed and recorded using a small animal activity recorder. When the mouse showed increased activity, irritability, lack of circadian rhythm, and continuous activity during the day and night, the model was considered successful. The body weight changes of each group of mice were measured and recorded.

[0069] 1.2 Grouping and administration

[0070] Rats were randomly divided into a control group (control group, 10 rats), a ventricular arrhythmia group (VA group, 10 rats), an Example 1 group (NHP group, 10 rats), a Comparative Example 1 group (OHP1 group, 10 rats), a Comparative Example 2 group (OHP2 group, 10 rats), a Comparative Example 3 group (OHP3 group, 10 rats), a Comparative Example 4 group (OHP4 group, 10 rats), and an amiodarone group (CDA group, 10 rats). Amiodarone is a commercially available product. Modeling and gavage treatment were initiated simultaneously. To ensure the full absorption of the therapeutic drug, each ISO injection was performed 2 h after gavage administration. Rats in the control group and the model group were respectively gavaged with an equal volume of normal saline. After modeling, the rats in the Example 1 group, the comparative example groups, and the amiodarone group were respectively administered the drugs of Example 1, the comparative example drugs, and the positive drug amiodarone, and the administration was continued for 14 days. The administration concentrations of the Example 1 group and the comparative example groups were 150 mg·kg -1 ·d -1 , and the administration concentration of amiodarone was 0.005 g·mL -1 . Rats in the model group and the blank group were gavaged with normal saline once a day, 2 mL each time, and the administration was continued for 14 days.

[0071] 1.3 Detection methods

[0072] Electrocardiogram detection: On the 14th day after administration, all rats were weighed and anesthetized with chloral hydrate at a dose of 0.3 mL / 100 g. Connect the PowerLab 15T multi-channel physiological recorder. Place the rat in a supine position on a wooden board, fix the four limbs with rubber bands, insert the metal needle into the subcutaneous tissue of the four disinfected limbs, dip the end of the lead in a little saline and clip it to the exposed end of the needle, measure the electrocardiogram of lead II, and dynamically observe for 30 min.

[0073] 1.4 Observation of the sleep time induced by suprathreshold dose of pentobarbital sodium in mice

[0074] Mice in each group were intraperitoneally injected with 2% pentobarbital sodium (40 mg·mL -1 ) 1 h after administration on the 13th day, and the sleep latency and sleep duration of the mice were observed and recorded. Sleep latency: The time from drug administration to the disappearance of the righting reflex in mice; Sleep duration: The time from the disappearance of the righting reflex to the recovery again in mice. When the mouse starts to fall asleep, place the mouse on a cushion with its abdomen facing up. Consider the disappearance of the righting reflex as the onset of sleep and the restoration of the righting reflex as awakening; If it is uncertain whether the righting reflex is restored, immediately place the mouse on its back flat after the first righting. If it rights itself automatically within 1 min, the time measured for the first time is the restoration time, otherwise, use the second righting time as the standard.

[0075] 1.5 Determination of the contents of glutamate (Glu) and γ-aminobutyric acid (GABA) in the brains of mice by ELISA

[0076] Immediately after the mice regained consciousness, they were sacrificed by cervical dislocation. The brains were removed, placed in cryotubes, and immediately immersed in liquid nitrogen, then transferred to an -80 °C refrigerator for storage. Before detection, the brain tissues were taken out and allowed to reach room temperature. 150 mg of brain tissue was precisely weighed, rinsed thoroughly with PBS, and the excess liquid was blotted dry with filter paper. 1.5 mL of lysis buffer was added, and the tissue was crushed and homogenized separately under ice bath conditions to prepare a 10% brain tissue homogenate. It was centrifuged at 13,000 r·min -1 for 2 times at 4 °C, 5 min each time; the supernatant of the brain tissue was taken, and the protein was quantitatively determined to be 5 mg·mL -1 by the BCA method; then, according to the steps of the ELISA kit instructions, the contents of Glu and GABA in the brain tissue were measured respectively, and the Glu / GABA ratio was calculated.

[0077] 2. Experimental results

[0078] 2.1 Evaluation of ventricular arrhythmia indicators

[0079] Table 1 QTc, PR interval, and QRS complex duration of rats in each group

[0080]

[0081]

[0082] Note: Compared with the control group, #, p < 0.05. Compared with the VA group, *, p < 0.05; **, p < 0.01; compared with the OHP group, Δ, p < 0.05.

[0083] Table 2 Onset time of ventricular premature beats (VP), ventricular tachycardia (VT), ventricular fibrillation (VF), and arrhythmia score in each group

[0084]

[0085] Note: Compared with the control group, #, p < 0.05. Compared with the VA group, *, #, p < 0.05; **, p < 0.01; compared with the OHP group, Δ, p < 0.05.

[0086] In this experiment, compared with the control group, the QTc, PR interval, and QRS complex duration of ventricular arrhythmia in the model group (VA group) were significantly increased. The values in the Example 1 group (NHP) and the amiodarone (CDA) group were significantly decreased, and the differences were statistically significant (p < 0.01). Compared with the VA group, in the drug administration groups, the Comparative Example 4 group (OHP4 group) failed to improve the ventricular arrhythmia indicators induced by isoproterenol, while the positive drug amiodarone group (CDA group) and Example 1 (NHP) significantly improved the indicators related to ventricular arrhythmia (p < 0.01), and the results were statistically significant; Comparative Examples 1-3 had no therapeutic effect.

[0087] 2.2 Evaluation of sleep-promoting function

[0088] After injection of sodium pentobarbital, mice in each group showed different degrees of sleep state. Compared with the control group, the sleep latency of mice in the VA group was significantly prolonged ( Figure 1 , P < 0.01), and the sleep time was significantly shortened ( Figure 2 , p < 0.01), indicating that PCPA-induced insomnia mice showed insomnia symptoms such as long sleep latency and short sleep time. Compared with the VA group, the sleep latency of mice in the NHP group was significantly shortened (p < 0.01), and the sleep time was significantly prolonged (p < 0.01); however, the OHP4 group and the positive drug CDA group had no such effect; Comparative Examples 1-3 had no therapeutic effect.

[0089] 2.3 Body weight evaluation

[0090] As Figure 3 shown, compared with the control group, the body weight of mice in the VA group was significantly reduced (p < 0.01). Compared with the VA group, the body weight of mice in the NHP group increased significantly, while the OHP4 group and the positive drug CDA group had no difference from the VA group (p < 0.05, p < 0.01); Comparative Examples 1-3 had no therapeutic effect.

[0091] 2.4 Contents of glutamate (Glu) and γ-aminobutyric acid (GABA) in the brain

[0092] Table 3 Contents of glutamate (Glu) and γ-aminobutyric acid (GABA) in the brain

[0093]

[0094] Note: Compared with the control group, #, p < 0.05. Compared with the VA group, *, p < 0.05; **, p < 0.01, ***, p < 0.001; compared with the OHP group, Δ, p < 0.05, ΔΔ, p < 0.01; compared with the NHP group, л, p < 0.05; лл, p < 0.01, ллл, p < 0.001; лллл, p < 0.0001.

[0095] Compared with the control group, the levels of Glu and Glu / GABA in the brains of rats in the VA group were significantly increased (p < 0.01), while the level of GABA was significantly decreased (p < 0.01). Compared with the VA group, the levels of Glu and Glu / GABA in the NHP group were significantly decreased (p < 0.01), while the levels of GABA were significantly increased (p < 0.01); there were no differences between the OHP4 group and the CDA group and the model group (p < 0.05, p < 0.01). The raphe nuclei in the midline of the brainstem mainly project to the forebrain and are used to regulate the sleep-wake state. Glu and GABA are important neurotransmitters involved in the sleep-wake mechanism. Glu is an excitatory neurotransmitter and plays an important role in maintaining wakefulness; GABA is an inhibitory neurotransmitter and plays a sedative and hypnotic role; the Glu / GABA ratio regulates the balance of neural excitation and inhibition, so it is often used to study and evaluate the excitatory and inhibitory states of the central nervous system. The new formula can promote sleep by regulating the imbalanced neuromodulation by reducing the content of the excitatory neurotransmitter Glu and the Glu / GABA ratio and increasing the content of the inhibitory neurotransmitter GABA in insomniac rats; the OHP1, OHP2, and OHP3 groups had no therapeutic effects.

[0096] The results of this study indicate that there are significant differences between the original formula and the new formula in the direction of treating ventricular arrhythmia. The traditional Chinese medicine composition of Example 1 can improve various indicators of ventricular arrhythmia through various means such as autonomic nerve regulation and promoting sleep.

[0097] It was verified that the therapeutic effects of the traditional Chinese medicine compositions of Example 2 and Example 3 were similar to those of Example 1.

[0098] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating ventricular arrhythmia, characterized in that: The traditional Chinese medicine composition comprises ginseng, ganoderma lucidum, safflower, musk, bezoar, bear bile, pearl, bufotoxin, aconite root and borneol; wherein, the mass ratios of ginseng, pearl and ganoderma lucidum are independently 11% to 70%.

2. The application according to claim 1, characterized in that: The mass ratios of ginseng, pearl and ganoderma lucidum are 11% to 46%, 11 to 41%, and 22% to 70% respectively.

3. The application according to claim 1, wherein: In terms of parts by mass, the traditional Chinese medicine composition comprises 700 to 1500 parts of ginseng, 10 to 50 parts of musk, 5 to 50 parts of bezoar, 5 to 50 parts of bear bile, 20 to 60 parts of bufotoxin, 700 to 1500 parts of pearl, 5 to 20 parts of borneol, 700 to 1500 parts of ganoderma lucidum, 50 to 120 parts of safflower, and 5 to 15 parts of aconite root.

4. The application according to claim 1, characterized in that: In terms of parts by mass, the traditional Chinese medicine composition comprises 750 to 1500 parts of ginseng, 15 to 50 parts of musk, 10 to 50 parts of bezoar, 8 to 50 parts of bear bile, 25 to 60 parts of bufotoxin, 750 to 1450 parts of pearl, 8 to 20 parts of borneol, 750 to 1450 parts of ganoderma lucidum, 60 to 110 parts of safflower, and 7 to 15 parts of aconite root.

5. The application according to claim 1, wherein: In terms of parts by mass, the traditional Chinese medicine composition comprises 200 to 400 parts of ginseng, 10 to 60 parts of musk, 5 to 50 parts of bezoar, 5 to 50 parts of bear bile, 20 to 60 parts of bufotoxin, 200 to 350 parts of pearl, 5 to 20 parts of borneol, 400 to 600 parts of ganoderma lucidum, 5 to 20 parts of aconite root, and 20 to 150 parts of safflower.

6. The application according to claim 1, wherein: The prevention and treatment of ventricular arrhythmia include the prevention and / or treatment of ventricular arrhythmia; preferably, the prevention and treatment of ventricular arrhythmia include improving at least one of the occurrence time of premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation.

7. The application according to claim 6, wherein: The prevention and treatment of ventricular arrhythmia include the prevention and / or treatment of ventricular arrhythmia by improving sleep.

8. The application according to claim 7, wherein: The improvement of sleep includes the improvement of at least one efficacy index such as sleep latency, sleep duration, Glu, GABA, and Glu / GABA levels in the brain tissue.

9. The application according to claim 1, wherein: The traditional Chinese medicine composition further comprises pharmaceutically acceptable excipients.

10. The application according to claim 1, characterized in that: When the traditional Chinese medicine composition is in the form of pills, the preparation method of the traditional Chinese medicine composition comprises the following steps: Sprinkle and mix the powders of each component raw material medicine, and spray water to obtain the pill of the traditional Chinese medicine composition.

Images