CN113476526B

CN113476526B - A Chinese medicinal composition for treating atrial fibrillation, and its preparation method

Info

Publication number: CN113476526B
Application number: CN202110921879.3A
Authority: CN
Inventors: 王新东; 张蒙; 毛晨晗
Original assignee: Jiangsu Provincial Insititute of Traditional Chinese Medicine
Current assignee: Jiangsu Provincial Insititute of Traditional Chinese Medicine
Priority date: 2021-08-12
Filing date: 2021-08-12
Publication date: 2022-03-29
Anticipated expiration: 2041-08-12
Also published as: CN113476526A

Abstract

The invention discloses a traditional Chinese medicine compound composition with a treatment effect on atrial fibrillation and a preparation method thereof, wherein the traditional Chinese medicine compound composition comprises the following traditional Chinese medicine decoction pieces in parts by mass: 10-20 parts of roasted stiff silkworm, 10-20 parts of scorpion, 5-10 parts of amber powder, 10-20 parts of radix rehmanniae recen, 20-30 parts of ginseng, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 5-10 parts of coptis chinensis, 20-30 parts of roasted turtle shell, 5-10 parts of cinnamon and 10-20 parts of lithospermum. The invention aims at the basic pathogenesis of deficiency of heart-yin and kidney-yin, deficient wind stirring, heart fire internal flaming, wind fire mutual pulsation, qi and yin consumption and palpitation, tachycardia and irregular pulse, establishes the therapeutic principle and treatment method of clearing heart and cooling blood and nourishing yin and calming wind, and provides the traditional Chinese medicine compound which has the effects of clearing heart and cooling blood and nourishing yin and calming wind.

Description

A Chinese medicinal composition for treating atrial fibrillation, and its preparation method

Technical Field

The invention belongs to a traditional Chinese medicine compound composition, and particularly relates to a traditional Chinese medicine compound composition with an atrial fibrillation treatment effect and a preparation method thereof.

Background

Atrial Fibrillation (Atrial Fibrillation) is a clinically common arrhythmia, the incidence of which rapidly increases with age, and is a high risk factor for the increase of the population's all-cause mortality, morbidity and readmission rates. The Framingham research result shows that the accumulated risk of atrial fibrillation of people in 10 years exceeds 15%, the risk of atrial fibrillation is 1.0% in the age group less than 65 years old and is 26.9% in the age group more than 65 years old, and therefore, about 800-1000 ten thousand of patients suffering from atrial fibrillation in China are estimated. The risk of an atrial fibrillation episode, which may induce or aggravate heart failure, is one of the independent risk factors for increased mortality in patients with organic heart disease, mainly results from thromboembolic events and heart failure, especially in patients with organic heart disease. In addition, atrial fibrillation is one of the leading causes of stroke, and in the crowd of 65 years old or older, 1/3's stroke is caused by atrial fibrillation, and the risk of atrial fibrillation patient thromboembolism complication increases 5~ 7 times, and is showing to increase disability rate and lethality rate. With the aging society, the high prevalence of atrial fibrillation, high mortality, and high disability rate create a huge medical burden. Therefore, exploring the mechanism of occurrence of atrial fibrillation, seeking safe and effective early intervention methods, and reducing the onset and recurrence of atrial fibrillation are hot and difficult points in the current cardiovascular disease research field. Unfortunately, since the upstream mechanisms of atrial fibrillation onset are not well understood, there is currently no clear effective primary or secondary prevention of atrial fibrillation attack. Moreover, the long-term effectiveness of atrial fibrillation therapy is limited by the potential side effects of traditional antiarrhythmic drugs, the risk of bleeding from long-term anticoagulation, and the high long-term recurrence rate of radiofrequency ablation.

The traditional Chinese medicine has diagnosis and treatment experience of more than two thousand years aiming at palpitation caused by atrial fibrillation. The advantages of multiple targets and low side reaction of the traditional Chinese medicine meet the requirements of long-range, multiple targets and low side reaction of first-level and second-level prevention and treatment of atrial fibrillation, and the medicine is a treasure house for searching and developing medicines for preventing and treating atrial fibrillation. Aiming at the clinical characteristics of sudden onset of atrial fibrillation, tachycardia and arrhythmia, the applicant provides the pathogenesis recognition of yin deficiency and pneumatosis, wind-fire fighting and qi-yin consumption injury, and adopts corresponding traditional Chinese medicine compound treatment, so that the clinical curative effect is obvious.

Disclosure of Invention

Object of the Invention

Aiming at the difficulty of clinical prevention and treatment of atrial fibrillation, provides a traditional Chinese medicine compound composition which has a treatment effect on atrial fibrillation and has the effects of clearing away heart-fire, cooling blood, nourishing yin and calming endogenous wind and a preparation method thereof.

Adopts the technical proposal

In order to realize the aim, the effective components and the parts by mass of the traditional Chinese medicine compound composition developed by the invention are as follows: 10-20 parts of roasted stiff silkworm, 10-20 parts of scorpion, 5-10 parts of amber powder, 10-20 parts of radix rehmanniae recen, 20-30 parts of ginseng, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 5-10 parts of coptis chinensis, 20-30 parts of roasted turtle shell, 5-10 parts of cinnamon and 10-20 parts of lithospermum.

The preparation method of the traditional Chinese medicine compound composition comprises the following steps: (1) grinding amber into fine powder according to the mass parts; (2) taking the processed stiff silkworm, the scorpion, the dried rehmannia root, the ginseng, the sophora flavescens, the salvia miltiorrhiza, the coptis chinensis, the processed turtle shell, the cinnamon and the lithospermum decoction pieces according to the mass parts, adding water for decocting twice, 1-2 hours each time, combining the decoctions, filtering, concentrating the filtrate, adding ethanol with the volume concentration of 85% for carrying out alcohol precipitation treatment, filtering out precipitates, recovering the filtrate, and concentrating the filtrate at 80 ℃ until the relative density is 1.30-1.36 to obtain an extract; (3) and (3) adding the fine powder obtained in the step (1) into the extract obtained in the step (2). Mixing the obtained extract with pharmaceutically acceptable vehicle, and making into unguent, oral liquid, granule, capsule, tablet or dripping pill.

The invention relates to a traditional Chinese medicine compound composition for treating atrial fibrillation, which is used for determining the treatment principle and treatment method of clearing heart-fire, cooling blood, nourishing yin and stopping endogenous wind aiming at the basic pathogenesis of atrial fibrillation, yin deficiency of heart and kidney, internal stirring of deficient wind, internal flaming of heart fire, mutual pulsation of wind and fire, consumption of qi and yin and irregular pulse. In the formula, the batryticated silkworm is matched with the scorpion to dispel wind and calm convulsion, and the turtle shell nourishes kidney and subdues yang, and the three are combined to play the role of nourishing yin and calming endogenous wind, which is the monarch drug; the coptis root and the sophora flavescens enter heart channels, and the compatibility of the coptis root and the sophora flavescens plays the role of clearing heat and calming heart together, and is taken as a ministerial drug. The ginseng is used for supplementing heart qi, the rehmannia root is used for clearing heat and cooling blood to nourish heart yin, the salvia miltiorrhiza is used for cooling blood and activating blood, and the amber powder is used for calming heart and tranquilizing mind. Cinnamon bark, cortex Cinnamomi, combined with Huang Lian, can communicate heart and kidney and induce fire to return to its original origin. The medicines are used together to play the effects of clearing heart fire, tonifying heart qi, calming heart spirit, nourishing kidney yin, calming deficient wind, relieving palpitation and regulating pulse.

Advantageous effects

The traditional Chinese medicine compound composition can obviously reduce the recurrence frequency and recurrence rate of atrial fibrillation of patients with paroxysmal atrial fibrillation, can obviously improve the clinical symptoms of palpitation, chest distress, dizziness, dry mouth, bitter taste, vexation, feverish palms and soles, spontaneous perspiration or night sweat and the like of the patients with atrial fibrillation, has definite curative effect on treating atrial fibrillation (heart-kidney yin deficiency and heart-fire internal flaming syndrome), and has small toxic and side effects after long-term administration and safe and reliable medication.

Detailed Description

The Chinese medicinal compound composition is applied to treating the symptoms of atrial fibrillation with yin deficiency of heart and kidney and internal flaming of heart fire, and clinically showing palpitation, vexation, dry or bitter mouth, hyperhidrosis, hypodynamia, dizziness, insomnia, red tongue with thin and yellow coating or little coating, fine and rapid pulse irregular pulse and the like.

The specific method comprises the following traditional Chinese medicine decoction piece components in parts by weight: 10-20 parts of roasted stiff silkworm, 10-20 parts of scorpion, 5-10 parts of amber powder, 10-20 parts of radix rehmanniae recen, 20-30 parts of ginseng, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 5-10 parts of coptis chinensis, 20-30 parts of roasted turtle shell, 5-10 parts of cinnamon and 10-20 parts of lithospermum.

The treatment effect of the Chinese herbal compound composition for treating atrial fibrillation according to the present invention is illustrated by the following clinical test examples.

1. Clinical data and methods

57 patients suffering from heart-kidney yin deficiency of atrial fibrillation and heart-fire internal flaming syndrome (14 patients suffering from persistent atrial fibrillation and 43 patients suffering from paroxysmal atrial fibrillation) who are diagnosed in the Xin-Yang medical university affiliated Chinese and western medicine combined hospital and meet the inclusion standard between 2016 and 2021 and 06 months are selected as study objects, and the study objects are divided into 32 traditional Chinese medicines and 25 control groups according to a random digital table method and the tolerance and the taking willingness of the patients to the traditional Chinese medicines.

(1) Diagnostic criteria

Western diagnostic criteria: refer to the AHA/ACC/HRS atrial fibrillation treatment guidelines 2014; the traditional Chinese medicine diagnosis standard is as follows: the diagnosis standard of the syndrome of yin deficiency of heart and kidney and internal flaming of heart-fire is formulated according to the national Standard of the people's republic of China-syndrome part of clinical diagnosis and treatment terminology of traditional Chinese medicine (GB/T16751.2-1997). The main symptoms are: palpitation, chest distress, syncope or dizziness, dry mouth, bitter mouth, vexation and feverish palms and soles. The secondary symptoms are as follows: spontaneous sweating and night sweating. Tongue pulse: red tongue with thin and yellow coating or little coating, thready and rapid pulse or irregular pulse.

(2) Inclusion criteria

The diagnosis standard of the western medicine for atrial fibrillation is met; ② the medicine accords with the diagnosis standard of the deficiency of heart-kidney yin and the internal flaming of heart fire in traditional Chinese medicine; age 30-70 years old; (iv) an electrocardiogram or a dynamic electrocardiogram and the like are recorded in the first 6 months of the group, and the episode of atrial fibrillation is definitely recorded for more than 30 s.

(3) Exclusion criteria

Firstly, atrial fibrillation related to serious valvular heart disease; atrial fibrillation associated with hyperthyroidism; atrial fibrillation is associated with cerebrovascular accident. ② the fraction of the left ventricular ejection is less than 35 percent, and the cardiac function classification of New York is grade III or IV. ③ anticoagulation contraindication. And fourthly, combining thrombus in the left atrium. Sick sinus syndrome, atrioventricular or bundle branch block. Sixthly, the pregnant or nursing women. Seventhly, allergic constitution and allergic to the herbs. Combining patients with serious primary diseases such as cerebrovascular diseases, liver diseases, kidney diseases, hemopoietic system diseases and the like, and patients with mental diseases.

(4) Method of treatment

The traditional Chinese medicine comprises: the Chinese medicinal compound granules are taken by subpackaging 10g per bag, one bag is taken in the morning and evening, and the Chinese medicinal compound granules are dissolved in warm boiled water for 30 minutes after a meal.

And the western medicine control group comprises: the metoprolol sustained-release tablet (Asricon, Sweden, Chinese medicine standard J20150044) is given, 23.75-95 mg.d^-1Taking the medicine immediately; or amiodarone hydrochloride tablet (Xenoffy, France, national standard H19993254), 0.2 g. d^-1Maintaining the dose, and taking the medicine immediately; or propafenone hydrochloride tablets (Shanghai, China and West three-dimensional pharmaceutical industry Co., Ltd., national Standard H31020452) of 300-600 mg d^-1The dosage is maintained, and the oral administration is carried out for 2-3 times.

The treatment course of the two groups is 24 weeks. During the treatment period, basic medicines for treating cardiovascular diseases such as hypertension and dyslipidemia can be applied correspondingly, and other anti-arrhythmia medicines with Chinese and western medicines are forbidden. The acute attack stage is treated by amiodarone or propafenone or electrical cardioversion. If paroxysmal atrial fibrillation lasts for 48 hours, warfarin (Shanghai Xin Ying, Chinese medicine standard H31022123) is administered to both groups, and the dosage is adjusted according to the international standard ratio, so as to maintain the international standard ratio between 2.0 and 3.0, or rivaroxaban tablets (Bayer, Germany, Chinese medicine)Quasi-character J20180076) 15-20 mg.d^-1And (4) anticoagulant treatment.

(5) Observation indicator and method

Electrocardiograms and dynamic electrocardiograms were recorded before treatment and every 4 weeks after the start of treatment in both groups. Echocardiography examination was performed before treatment, 24 weeks after treatment.

(ii) recurrence rate and frequency of recurrence of paroxysmal atrial fibrillation the recurrence of paroxysmal atrial fibrillation is defined as a second episode of atrial fibrillation within the observation period. And (3) recording the number of recurrent atrial fibrillation patients in the observation period of two groups of patients with paroxysmal atrial fibrillation by follow-up visit, and calculating the recurrence rate, wherein the recurrence rate is the number of recurrent atrial fibrillation patients, and the number of recurrent atrial fibrillation patients is multiplied by 100%. The number of episodes of atrial fibrillation per relapsing patient during the observation period was defined as the number of relapses.

② the echocardiogram adopts Vivid color Doppler ultrasonic diagnostic apparatus of GE company in America, the probe frequency is 3.5 Hz. The patient takes the left lateral decubitus and collects the long axis, the short axis (the level of the mitral valve, the level of papillary muscle and the level of the apex of the heart) and the apex (the level of the two-cavity, three-cavity and four-cavity heart) two-dimensional ultrasonic sections of the left ventricle beside the sternum. Left ventricular end-diastolic measurement (LAD), Left Ventricular Ejection Fraction (LVEF), Left ventricular end-diastolic measurement (LVEDD) were obtained from a parasternal Left ventricular long axis section.

③ the clinical curative effect judgment standard shows the effect: paroxysmal AF does not occur at all or occasionally occurs, and persistent AF repeats or becomes paroxysmal AF occasionally occurring; or the ventricular rate is less than 80 times/min in a resting state. The method has the following advantages: paroxysmal AF outbreaks are reduced by more than 60 percent, the time of the outbreaks and the frequency of the outbreaks are included, and the persistent AF is converted into the paroxysmal AF; or the ventricular rate is less than 90 times/min in a resting state. And (4) invalidation: those who do not meet the above criteria of effectiveness or effectiveness.

The standard of the curative effect of the syndrome of the traditional Chinese medicine is formulated according to the guiding principle of clinical research of new traditional Chinese medicines, the integral method is adopted, the main symptoms are respectively scored as 0, 2, 4 and 6 according to the absence, lightness, middle and weight of symptoms, the secondary symptoms are respectively scored as 0, 1, 2 and 3 according to the absence, lightness, middle and weight of symptoms, and the tongue and pulse conditions are respectively scored as 0 and 1 according to the normality and abnormality. Efficacy index is (pre-treatment total score-post-treatment total score) ÷ pre-treatment total score. The curative effect is judged according to the following standards: the method has the following advantages: the symptoms are obviously improved, and the syndrome score is reduced by more than or equal to 70 percent compared with the syndrome score before treatment; secondly, the method is effective: the symptoms are improved, and the syndrome score is reduced by more than or equal to 30 percent and less than 70 percent compared with the syndrome score before treatment; ③ invalid: symptoms are not improved, and the syndrome score is reduced by less than 30 percent compared with the syndrome score before treatment; weighting: the symptoms worsen, and the syndrome score decreases by less than 0% compared with the former.

(6) Statistical method

Statistical analysis is carried out on the collected data by adopting SPSS 21 statistical software, and if the measured data conforms to normal distribution, the mean value plus or minus standard deviation is used

In this case, the paired sample t test was used for the intra-group comparison, and the independent sample t test was used for the inter-group comparison. Expressing the data rate and composition ratio by using χ²And (6) checking. The difference is statistically significant when P is less than 0.05.

2. Results

(1) The traditional Chinese medicine compound composition can reduce the recurrence frequency and recurrence rate of patients with paroxysmal atrial fibrillation

The relapse number and the relapse rate of the traditional Chinese medicine paroxysmal atrial fibrillation patients are lower than those of a control group, and the statistical difference is realized (P is less than 0.05). The relapse frequency of the traditional Chinese medicine group is obviously lower than that of the control group, and the difference has statistical significance (P is less than 0.05). The results are shown in Table 1.

TABLE 1 comparison of frequency and rate of recurrence in two groups

Note: x channel X²Inspection, χ²5.204, P < 0.05; compared with the control group, the compound of the formula,^#P＜0.05

(2) the clinical curative effect and the traditional Chinese medicine syndrome curative effect of the traditional Chinese medicine compound composition are obviously superior to those of pure western medicine treatment

The clinical total effective rate of the traditional Chinese medicine is superior to that of a control group, the difference has statistical significance, and the result is shown in a table 2; the total effective rate of the traditional Chinese medicine symptoms of the traditional Chinese medicine group is obviously superior to that of the control group, the difference has statistical significance, and the result is shown in table 3.

TABLE 2 two groups of clinical efficacy comparison/example

Note: jingchi type²Inspection, χ²＝4.131，P＜0.05

TABLE 3 two comparative/examples of the curative effects of TCM syndrome

Note: jingchi type²Inspection, χ²＝5.027，P＜0.05

(3) The traditional Chinese medicine compound composition can obviously reduce the single syndrome integral of the traditional Chinese medicine principal symptoms

After the treatment of the traditional Chinese medicine group, the score of the main symptoms such as palpitation, chest distress, dizziness, dry mouth, bitter taste in mouth, vexation, feverish palms and soles, spontaneous perspiration or night sweat, tongue pulse and the like are all obviously reduced (P is less than 0.05 or P is less than 0.01), and after the treatment of the control group, the score of the main symptoms except the score of the palpitation and the chest distress is reduced, and the score of the main symptoms has no obvious change. The score of the main symptoms of the two groups after treatment is compared, and the score of the main symptoms of the traditional Chinese medicine except palpitation is lower than that of a control group (P is less than 0.05 or P is less than 0.01). The results are shown in Table 4.

TABLE 4 comparison of single syndrome before and after treatment

Note: group comparisons,. P < 0.01; comparison between groups # P < 0.01, # # P < 0.05.

(4) The traditional Chinese medicine compound composition can improve partial cardiac function parameters

LVEDD before and after treatment of the traditional Chinese medicine and the control group is obviously reduced, the difference has obvious statistical significance (P is less than 0.01), and no obvious statistical difference exists between the groups; comparison differences between before and after treatment and between the LAD and LVEF groups were not statistically significant, and the results are shown in Table 5.

TABLE 5 comparison of two sets of cardiac function parameters

Note: the comparison is carried out in the group,^**P＜0.01。

Claims

1. the traditional Chinese medicine compound composition with the effect of treating atrial fibrillation is characterized by comprising the following components in parts by mass: 10-20 parts of roasted stiff silkworm, 10-20 parts of scorpion, 5-10 parts of amber powder, 10-20 parts of radix rehmanniae recen, 20-30 parts of ginseng, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 5-10 parts of coptis chinensis, 20-30 parts of roasted turtle shell, 5-10 parts of cinnamon and 10-20 parts of lithospermum.

2. The compound Chinese medicinal composition for treating atrial fibrillation according to claim 1, wherein the preparation method comprises the following steps: (1) grinding amber into fine powder according to the mass parts; (2) taking the processed stiff silkworm, the scorpion, the dried rehmannia root, the ginseng, the sophora flavescens, the salvia miltiorrhiza, the coptis chinensis, the processed turtle shell, the cinnamon and the lithospermum decoction pieces according to the mass parts, adding water for decocting twice, 1-2 hours each time, combining the decoctions, filtering, concentrating the filtrate, adding ethanol with the volume concentration of 85% for carrying out alcohol precipitation treatment, filtering out precipitates, recovering the ethanol from the filtrate, and concentrating the filtrate at 80 ℃ until the relative density is 1.30-1.36 to obtain an extract; (3) and (3) adding the fine powder obtained in the step (1) into the extract obtained in the step (2), and preparing the mixture and a pharmaceutically acceptable carrier into a medicament in the dosage form of paste, oral liquid, granules, capsules, tablets or pills.

3. The traditional Chinese medicine compound composition of claim 1 is prepared into a medicament in the dosage form of paste, oral liquid, granules, capsules, tablets or pills according to the method of claim 2.