Cupressaceae plant extract and its application in preparing medicine for preventing and treating arrhythmia

Abstract

The invention discloses a Cupressaceae plant extract and its application in preparing arrhythmia prevention and treatment medicine. The invention finds that the alcohol extract of Platycladus orientalis, Japanese cypress or Japanese juniper (Xinjiang juniper) has good prevention and treatment effect on arrhythmia and can be used to prepare corresponding medicines to prevent and treat patients with arrhythmia.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a Cupressaceae plant extract and application thereof in the preparation of arrhythmia prevention and treatment medicines. Background Art

[0002] Arrhythmia refers to the abnormality of the frequency, rhythm, origin, conduction speed or excitement order of cardiac impulses, and is an important group of cardiovascular diseases. Arrhythmia is often clinically divided into fast arrhythmia and slow arrhythmia according to the speed of the heart rate when it occurs; fast arrhythmia includes sinus tachycardia, atrial premature beats (atrial tachycardia, atrial flutter, atrial fibrillation), ventricular premature beats (bigemmythmia, ventricular flutter, ventricular fibrillation, etc.), and slow arrhythmia includes sinus arrest, first-degree atrioventricular block, second-degree atrioventricular block, third-degree atrioventricular block, etc. The clinical manifestations of arrhythmia are mainly palpitations, panic, chest tightness, chest pain, shortness of breath, fatigue, dyspnea, dizziness and other symptoms. The main hazard is to reduce the ejection of the heart. Severe arrhythmia can even cause patients to have low blood pressure, shock, etc. Some can cause Ass syndrome attacks, causing patients to become comatose, unconscious, limb convulsions, and even sudden death. The success rate of treatment for sudden cardiac death (the most serious arrhythmia) is less than 1%. Even in developed countries, with good treatment equipment and well-trained professionals, the success rate of treatment for sudden cardiac death is less than 5%. Therefore, it is crucial to seek safe, fast and effective antiarrhythmic drugs.

[0003] Currently, there are four types of antiarrhythmic drugs commonly used in clinical practice. Class I drugs block fast sodium channels and are divided into subclasses Ia, Ib, Ic, and Ic according to the intensity of sodium channel blocking and the time constant of channel resurrection after blocking. They are represented by quinidine, lidocaine, and propafenone, respectively. Class II drugs block β-adrenergic receptors, represented by metoprolol and atenolol. Class III drugs block potassium channels and prolong repolarization, represented by amiodarone and sotalol. Class IV drugs block slow calcium channels, represented by verapamil and diltiazem. Among these four categories, amiodarone is the most widely used antiarrhythmic drug in clinical practice. It is mainly suitable for various supraventricular (including atrial flutter and atrial fibrillation) and ventricular arrhythmias; it is especially suitable for arrhythmias with organic heart disease and heart failure after myocardial infarction. Its mechanism of action is mainly to block multiple ion channels. First, it can block potassium channels, inhibit the repolarization process, and prolong the effective refractory period of myocardial cells and the duration of action potentials. At the same time, it can mildly block sodium ion channels and calcium ion channels. In addition, it has mild antagonism of α and β adrenergic receptors, dilates blood vessels, and can be used to improve the symptoms of angina pectoris. The following adverse reactions often occur during the antiarrhythmic treatment of amiodarone: 1. Cardiovascular adverse reactions, common ones include sinus bradycardia, atrioventricular block, QT interval prolongation and hypotension, and even heart failure; 2. Gastrointestinal reactions, such as nausea, vomiting, loss of appetite, constipation, abnormal liver function (elevated transaminase); 3. Skin photosensitivity and facial pigmentation; 4. Hyperthyroidism or hypothyroidism may occur in a small number of people; 5. The most serious and rare change is pulmonary interstitial fibrosis; in addition, hypokalemia may occur, and the serum potassium level should be closely monitored during use.

[0004] At present, there are no reports or documents on the application and pharmacological effects of Cupressaceae plants in the prevention and treatment of arrhythmias. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a Cupressaceae plant extract and its application in preparing arrhythmia prevention and treatment medicine.

[0006] One of the technical solutions adopted by the present invention to solve the technical problem is:

[0007] A Cupressaceae plant extract, wherein the Cupressaceae plant includes at least one of Platycladus orientalis, Chamaecyparis obtusifolia or Sabina chinensis, and the extract is an alcohol extract of the leaves of the Cupressaceae plant.

[0008] Preferably, the extract is a 70-80% ethanol extract of the leaves of the Cupressaceae plant, which is prepared by the following method: taking the leaves of the Cupressaceae plant, adding 70-80% ethanol for soaking and extraction, and then drying the extract to obtain the Cupressaceae plant extract.

[0009] Preferably, the formula ratio of the leaves of the Cupressaceae plant to the 70-80% ethanol is 90-110 g: 450-550 mL.

[0010] Preferably, the soaking and extraction time is 3 to 7 days.

[0011] The second technical solution adopted by the present invention to solve its technical problem is:

[0012] A preventive medicine for arrhythmia, comprising the above-mentioned Cupressaceae plant extract.

[0013] The third technical solution adopted by the present invention to solve its technical problem is:

[0014] A therapeutic drug for arrhythmia, comprising the above-mentioned Cupressaceae plant extract.

[0015] Preferably, in the drug for preventing arrhythmia, the dosage of the drug, calculated based on the weight of the Cupressaceae plant extract, is 250-350 mg / 60 kg body weight; in the drug for treating arrhythmia, the dosage of the drug, calculated based on the weight of the Cupressaceae plant extract, is 250-350 mg / 60 kg body weight.

[0016] Preferably, the drug is in an oral dosage form.

[0017] Preferably, the Cupressaceae plant extract is dissolved in vegetable oil (preferably olive oil) to obtain the drug; or the Cupressaceae plant extract is combined with a pharmaceutically acceptable excipient or carrier and prepared into a powder, tablet, capsule or ointment, etc. using a pharmaceutically acceptable process.

[0018] In a preferred embodiment of the present invention, the method for preparing the extract of Platycladus orientalis, Japanese cypress and Japanese juniper comprises: cutting branches from Platycladus orientalis, Japanese cypress and Japanese juniper, washing and drying, picking leaves, weighing 100 grams of leaves of Platycladus orientalis, Japanese cypress and Japanese juniper, respectively, soaking them in 450-550 mL of 70-80% ethanol, ultrasonicating them, taking out the soaking liquid and drying it in a drying oven. Adults take it in a dosage of 300 mg / 60 kg, dissolving it in vegetable oil (preferably olive oil) to make it liquid. It can also be made into powder, tablets, capsules and ointments.

[0019] The fourth technical solution adopted by the present invention to solve its technical problem is:

[0020] The application of the Cupressaceae plant extract in preparing arrhythmia prevention medicine.

[0021] The fifth technical solution adopted by the present invention to solve the technical problem is:

[0022] The application of the Cupressaceae plant extract in preparing arrhythmia therapeutic medicine.

[0023] The Cupressaceae plants involved in the present invention specifically include:

[0024] Platycladus orientalis

[0025] Japanese cypress Chamaecyparis obtusa

[0026] Juniperus sabina, also known as Xinjiang juniper

[0027] Fokienia hodginsii

[0028] Juniperus chinensis 'Pyramidalis'

[0029] Sabina chinensis

[0030] Juniperus chinensis

[0031] Unless otherwise specified, the equipment, reagents, processes, parameters, etc. involved in the present invention are conventional equipment, reagents, processes, parameters, etc. and are not given as embodiments.

[0032] In the "pharmaceutically acceptable excipients or carriers" of the present invention, the excipients include but are not limited to diluents, solvents, excipients, absorbents, wetting agents, adhesives, disintegrants, lubricants, solubilizers, emulsifiers, suspending agents, surfactants, film-forming agents, propellants, antioxidants, flavoring agents, fragrances, bactericides, preservatives, etc.; the carrier refers to a system that has the functions of changing the way a compound enters the human body and its distribution in the body, controlling the release rate to achieve controlled release or sustained release, and targeted delivery to target organs, including but not limited to liposomes, microspheres, microcapsules, solid dispersions, micelles, microemulsions, gels, sustained-release carriers, controlled-release carriers, targeted carriers, nanoparticle materials, etc.

[0033] All ranges recited herein include all point values ​​within the range.

[0034] The terms “approximately”, “about” or “around” as used herein refer to within ±20% of the range or value.

[0035] In the present invention, when % is used to express concentration, unless otherwise specified, when the solute is a liquid, % represents volume percentage, and when the solute is a solid, % represents g / 100 mL.

[0036] Compared with the background technology, this technical solution has the following advantages:

[0037] The invention finds that 70-80% ethanol extracts of leaves of Platycladus orientalis, Japanese cypress and Sabina chinensis have obvious effects in preventing and treating arrhythmia, and can be used to prepare corresponding medicines to prevent and treat patients with arrhythmia. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 This is a normal electrocardiogram of mice and a blank control of Japanese cypress. It can be seen that administration of 0.10mL / 10g of 75% ethanol extract of Japanese cypress did not induce arrhythmia in mice.

[0039] Figure 2 This is the electrocardiogram of mice after being given olive oil. It can be seen that olive oil has no obvious effect on the heart rhythm of mice and does not induce arrhythmia.

[0040] Figure 3 This is the electrocardiogram of mice after being given barium chloride. It can be seen that barium chloride induced the arrhythmia bigeminy in mice.

[0041] Figure 4 Used to illustrate that administration of 0.10mL / 10g of 75% ethanol extract of Platycladus orientalis can prevent barium chloride-induced arrhythmias.

[0042] Figure 5 Used to illustrate that administration of 0.05 mL / 10 g of 75% ethanol extract of Japanese cypress did not prevent barium chloride-induced arrhythmias because the dose was too small.

[0043] Figure 6 It is used to illustrate that administration of 0.075 mL / 10 g of 75% ethanol extract of Japanese cypress did not prevent barium chloride-induced arrhythmia because the dose was small and the preventive effect could not be achieved.

[0044] Figure 7 Used to show that administration of 0.10mL / 10g of 75% ethanol extract of Japanese cypress can prevent barium chloride-induced arrhythmias.

[0045] Figure 8 Used to show that administration of 0.15mL / 10g of 75% alcohol extract of Japanese cypress can prevent barium chloride-induced arrhythmias.

[0046] Fig. 9 Used to show that administration of 0.10 mL / 10 g of 75% ethanol extract of Sabina chinensis can prevent barium chloride-induced arrhythmias.

[0047] Fig.10 Used to illustrate that administration of 0.10mL / 10g of 75% ethanol extract of Fukienanthes has no obvious preventive effect on barium chloride-induced arrhythmia.

[0048] Fig.11 Used to illustrate that administration of 0.10mL / 10g of 75% ethanol extract of Tuber has no significant preventive effect on barium chloride-induced arrhythmias.

[0049] Fig.12 Used to illustrate that administration of 0.10mL / 10g of 75% ethanol extract of arborvitae has no obvious preventive effect on barium chloride-induced arrhythmia.

[0050] Fig.13 Used to illustrate that administration of 0.10mL / 10g of 75% ethanol extract of Juniperus chinensis has no significant preventive effect on barium chloride-induced arrhythmias.

[0051] Fig.14 Used to illustrate that administration of 0.10mL / 10g olive oil has no significant therapeutic effect on barium chloride-induced arrhythmias.

[0052] Fig.15 Used to illustrate that administration of 0.6% amiodarone 0.10mL / 10g can treat barium chloride-induced arrhythmias.

[0053] Fig.16 Used to illustrate that administering 0.10mL / 10g of 75% ethanol extract of Platycladus orientalis can treat barium chloride-induced arrhythmias.

[0054] Fig.17 Used to illustrate that administration of 0.05 mL / 10 g of 75% ethanol extract of Japanese cypress cannot treat barium chloride-induced arrhythmias.

[0055] Fig.18 Used to illustrate that administration of 0.075 mL / 10 g of 75% ethanol extract of Japanese cypress cannot treat barium chloride-induced arrhythmias.

[0056] Fig.19 Used to illustrate that administration of 0.10mL / 10g of 75% ethanol extract of Japanese cypress can treat barium chloride-induced arrhythmias.

[0057] Fig. 20 Used to illustrate that administration of 0.15mL / 10g of 75% ethanol extract of Japanese cypress can treat barium chloride-induced arrhythmias.

[0058] Fig.21 Used to illustrate that administration of 0.20 mL / 10 g of 75% ethanol extract of Japanese cypress cannot treat barium chloride-induced arrhythmias.

[0059] Fig. 22 Used to illustrate that administration of 0.10 mL / 10 g of 75% ethanol extract of Sabina chinensis can treat barium chloride-induced arrhythmias.

[0060] Fig.23 It is used to illustrate that administration of 0.10 mL / 10 g of 75% ethanol extract of Fukienanthera has no obvious therapeutic effect on arrhythmia induced by barium chloride.

[0061] Fig.24 It is used to illustrate that administering 0.10mL / 10g of 75% ethanol extract of Tabernacle has no obvious therapeutic effect on arrhythmias induced by barium chloride. Bigeminy and ventricular tachycardia occur after injection of barium chloride, and the rescue effect of Tabernacle after oral gavage is poor.

[0062] Fig.25 It is used to illustrate that administering 0.10mL / 10g of 75% ethanol extract of arborvitae has no obvious therapeutic effect on arrhythmia induced by barium chloride. After barium chloride-induced arrhythmia, premature ventricular contractions and ventricular fibrillation occurred, and no improvement was seen after administering 0.10mL / 10g of 75% ethanol extract of arborvitae.

[0063] Fig.26 It is used to illustrate that administration of 0.10 mL / 10 g of 75% ethanol extract of Sabina has no obvious therapeutic effect on barium chloride-induced arrhythmia. DETAILED DESCRIPTION

[0064] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0065] Example

[0066] 1. Materials

[0067] 1.1 Experimental animals: 60 clean-grade ICR male mice, weighing 30±2 g, were purchased from Shanghai Wu Experimental Animal Center and fed with normal diet and drinking water to adapt to the environment for 1 week.

[0068] 1.2 Reagents and instruments: isoflurane, olive oil, 0.8% barium chloride solution, Platycladus orientalis, Japanese cypress, Juniperus chinensis, Fujian cypress, Taraxac, Chinese cypress, and Juniperus chinensis; anesthesia machine, BL-420I integrated and information-based acquisition and processing system (Chengdu Taimeng Software Co., Ltd.).

[0069] 2. Methods and Results

[0070] 2.1 Cupressaceae extract: Take branches cut from the trees of Platycladus orientalis, Japanese cypress, juniper, Fujian cypress, cedarwood, cypress, arborvitae, and juniper, wash and dry them, and pick off the leaves; weigh 100g of leaves of Platycladus orientalis, Japanese cypress, juniper, Fujian cypress, cedarwood, cypress, arborvitae, and juniper, respectively, add 500mL of 75% ethanol, soak for 3 to 7 days, and then ultrasonically treat (temperature 25°C, vibration frequency 100kHz), take out the soaking liquid and dry it in a drying oven, and dissolve the residue after drying with 1mL of olive oil to obtain 75% ethanol extracts of Platycladus orientalis, Japanese cypress, juniper, Fujian cypress, cedarwood, cypress, arborvitae, and juniper.

[0071] 2.2 Animal grouping: The experimental mice were randomly divided into a normal group, a control group (divided into a negative control group and a positive control group), and an experimental group (divided into a prevention group and a treatment group according to the purpose of the study), with 6 mice in each group. All mice were given normal diet and drinking water.

[0072] 2.3 Prevention effect investigation: The mice were weighed, anesthetized with isoflurane, and restrained on the mouse board in the supine position. The standard II lead electrocardiogram was recorded using the BL-420I integrated and information-based acquisition and processing system. The normal group was given physiological saline, the negative control group was given olive oil, and the experimental group (i.e., the prevention group) was given 75% ethanol extracts of Platycladus orientalis, Japanese cypress, fork cypress, Fujian cypress, cypress, cypress, and cypress, respectively, at 0.05mL / 10g, 0.075mL / 10g, 0.10mL / 10g, 0.15mL / 10g, and 0.20mL / 10g by gavage according to body weight. Ten minutes later, mice in different groups were intraperitoneally injected with BaCl 2 (0.1mL / 10g), the electrocardiogram was continuously monitored during the experiment to observe the time of arrhythmia. The experimental results showed that the 75% ethanol extracts of Platycladus orientalis (dose 0.10mL / 10g), Japanese cypress (dose 0.10-0.15mL / 10g), and Japanese juniper (dose 0.10mL / 10g) had a preventive effect on arrhythmia induced by barium chloride ( Figures 4 to 9 ), but the 75% ethanol extracts of Hokkien cypress, Tajun, Longbai, and Juniperus had no significant preventive effect on barium chloride-induced arrhythmias ( Figures 10 to 13 ).

[0073] The experiment was repeated, with amiodarone as the positive control group and 75% ethanol extracts of Platycladus orientalis, Japanese cypress, and Sabina chinensis as the experimental group (i.e., the preventive group). The mice were given 0.05 mL / 10 g, 0.075 mL / 10 g, 0.10 mL / 10 g, 0.15 mL / 10 g, and 0.20 mL / 10 g, respectively. Ten minutes later, the mice in different groups were intraperitoneally injected with BaCl 2 (0.1mL / 10g), the electrocardiogram was continuously monitored during the experiment to observe the time of arrhythmia. The experimental results show that the 75% ethanol extracts of the leaves of three types of Cupressaceae plants, namely Platycladus orientalis, Japanese cypress, and Sabina chinensis, have a preventive effect on arrhythmia induced by barium chloride, and the effect is more significant with the increase of the dose, with a significant difference (p<0.05). At the same time, compared with amiodarone, a commonly used antiarrhythmic drug in clinical practice, the effect is more obvious.

[0074] 2.4 Treatment effect investigation: The mice were weighed, anesthetized with isoflurane, and immobilized on a mouse board in the supine position. The standard II lead electrocardiogram was recorded using the BL-420I integrated and information-based acquisition and processing system. 2 (0.1mL / 10g), treated with olive oil; the positive control group was intraperitoneally injected with BaCl 2 (0.1 mL / 10 g), treated with 0.6% amiodarone 0.10 mL / 10 g; the experimental group (i.e., treatment group) was intraperitoneally injected with BaCl 2 (0.1mL / 10g) After arrhythmia occurred, the mice were treated by oral gavage with 75% ethanol extracts of Platycladus orientalis, Japanese cypress, Juniperus chinensis, Cupressus fujianensis, Taraxac, Cypress chinensis, and Juniperus chinensis at different doses (0.05mL / 10g, 0.075mL / 10g, 0.10mL / 10g, 0.15mL / 10g). During the experiment, the mice were continuously recorded with quasi-II lead electrocardiogram.

[0075] The experimental results showed that olive oil in the negative control group could not cure arrhythmia induced by barium chloride ( Fig.14 ); The positive control group 0.6% amiodarone 0.10mL / 10g can cure arrhythmias induced by barium chloride ( Fig.15 ); In the experimental group (i.e., the treatment group), 0.05 mL / 10 g of 75% ethanol extracts of Platycladus orientalis, Japanese cypress, and Japanese juniper could not restore the arrhythmia of mice to normal, but with the increase of the dose, the effect of the treatment of arrhythmia (the speed of onset and the duration of recovery to normal) increased significantly, and there was a significant difference (p<0.05). 0.10 mL / 10 g of Platycladus orientalis, 0.10-0.15 mL / 10 g of Japanese cypress, and 0.10 mL / 10 g of Japanese cypress had a therapeutic effect on arrhythmia induced by barium chloride ( Figures 16 to 22 ), but 0.10mL / 10g of 75% ethanol extracts of Fujian cypress, tower cypress, dragon cypress, and juniper had no significant therapeutic effect on barium chloride-induced arrhythmias ( Figure 23 to Figure 26 ).

[0076] The above description is only a preferred embodiment of the present invention, and therefore cannot be used to limit the scope of the present invention. That is, equivalent changes and modifications made according to the patent scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. Use of a Cupressaceae plant extract in preparing a preventive drug for arrhythmia, wherein the Cupressaceae plant is composed of at least one of Platycladus orientalis, Chamaecyparis obtusifolia or Thuja serrata, and the extract is an alcohol extract of leaves of the Cupressaceae plant; the extract is prepared by the following method: taking fresh leaves of the Cupressaceae plant, washing and drying them, adding 70-80% ethanol to soak and extract, and drying the extract to obtain the Cupressaceae plant extract; the formula ratio of the Cupressaceae plant leaves to the 70-80% ethanol is 90-110 g: 450-550 mL; the soaking extraction time is 3-7 days.

2. Use of a Cupressaceae plant extract in preparing a drug for treating arrhythmia, wherein the Cupressaceae plant is composed of at least one of Platycladus orientalis, Chamaecyparis obtusifolia or Thuja serrata, and the extract is an alcohol extract of leaves of the Cupressaceae plant; the extract is prepared by the following method: taking fresh leaves of the Cupressaceae plant, washing and drying them, adding 70-80% ethanol to soak and extract, and drying the extract to obtain the Cupressaceae plant extract; the formula ratio of the Cupressaceae plant leaves to the 70-80% ethanol is 90-110 g: 450-550 mL; the soaking extraction time is 3-7 days.

3. The use according to claim 1 or 2, Features: The dosage of the drug is calculated based on the weight of the Cupressaceae plant extract and is 250-350 mg / 60 kg body weight.

4. The use according to claim 1 or 2, Features: The medicine is in the form of oral administration.

5. The use according to claim 1 or 2, Features: The Cupressaceae plant extract is dissolved in vegetable oil to obtain the medicine; or the Cupressaceae plant extract is made into powder, tablet, capsule or paste.

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