CN101919854B - Application of thaliadine in preparing medicament for treating arrhythmia - Google Patents
Application of thaliadine in preparing medicament for treating arrhythmia Download PDFInfo
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- CN101919854B CN101919854B CN2009102329879A CN200910232987A CN101919854B CN 101919854 B CN101919854 B CN 101919854B CN 2009102329879 A CN2009102329879 A CN 2009102329879A CN 200910232987 A CN200910232987 A CN 200910232987A CN 101919854 B CN101919854 B CN 101919854B
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Abstract
The invention relates to an application method for thaliadine in preparing a medicament for treating arrhythmia. The thaliadine is used for preparing the medicament for treating the arrhythmia; and the prepared medicament can obviously resist the arrhythmia of chloroform induced mice, adrenaline induced rabbits, barium chloride induced rats and aconitine induced rats, and has remarkable effect.
Description
Technical field
The present invention relates to the application process of little Thalictrum aquilegifolium L. var. sibiricum Regel aldin, especially the application process in preparation treatment antiarrhythmic medicament.
Background technology
Little Thalictrum aquilegifolium L. var. sibiricum Regel aldin (Thaliadine) belongs to native compound, its molecular formula: C
30H
33NO
8, molecular weight: 535.593.Little Thalictrum aquilegifolium L. var. sibiricum Regel aldin mainly is present in the Ranunculaceae various plants, CAS accession number: 67510-96-7, and structural formula is as follows:
The Chinese medicine Thalictrum omeiense W. T. Wang et S. H. Wang is the herb of the high eyebrow Thalictrum aquilegifolium L. var. sibiricum Regel of ranunculaceae plant Thalictrum omeiense W.T.Wang et S.H.Wang.Effect with heat-clearing and toxic substances removing.Herb contains little Thalictrum aquilegifolium L. var. sibiricum Regel aldin.
Arrhythmia (Cardiac Arrhythmia) is common clinical, frequently-occurring disease, and serious arrhythmia is one of final cause of the death of patients such as myocardial hypertrophy, myocardial ischemia, myocardial infarction and heart failure.Arrhythmia is meant frequency, the rhythm and pace of moving things, origin position, conduction velocity and exciting order unusual of cardiac impulse.Common arrhythmia has sinus tachycardia, sinus bradycardia, arrhythmia, premature beat, paroxysmal tachycardia, atrial fibrillation, atrioventricular block etc.Clinically mainly show very then visible dizzy, dizzy, chest pain tachypnea, cold extremities due to sweating or collapse for it with cardiopalmus, palpitation with a distress feeling, abnormal pulse condition.Arrhythmia belongs to the category of traditional Chinese medical science cardiopalmus card.
Cause that ARR reason has a lot, common have cardiovascular disease, electrolyte disturbance, drug effect, infection and virus function, neural factor, an endocrine factors etc.ARR electrophysiological mechanism mainly contain impulsion generate unusual, conduction of impulse is unusual etc.
The traditional Chinese medical science thinks that the main etiology and pathogenesis of primary disease has: timidness due to deficiency of the heart, deficiency of heart-blood, hyperactivity of fire caused by deficiency of YIN, flaccidity of the heart-yang, diseases caused by retention of fluid are insulted the heart, obstruction of collaterals by blood stasis etc.
There is not little Thalictrum aquilegifolium L. var. sibiricum Regel aldin to disclose in the prior art as yet as the application of preparation treatment antiarrhythmic medicament.
Summary of the invention
The technical problem to be solved in the present invention is used the ARR medicine of little Thalictrum aquilegifolium L. var. sibiricum Regel aldin preparation treatment exactly.
In order to solve the problems of the technologies described above, the present invention adopts following technical proposal: little Thalictrum aquilegifolium L. var. sibiricum Regel aldin is as the application of preparation treatment antiarrhythmic medicament.
When the present invention was used for preparation treatment antiarrhythmic medicament, its oral or non-oral administration all was safely and effectively.Oral administration can be made any regular dosage form, as: powder, granule, capsule, sheet, oral cavity disintegration tablet, drop pill, soft capsule etc.; Non-oral administration can be made into various regular dosage forms, as injection etc.
When the present invention was used for preparation treatment antiarrhythmic medicament, its adjuvant and preparation method can be selected the acceptable form of any pharmacy for use.
Dosage of the present invention can change according to factors such as the mode of taking, patient's age, the degree that is in a bad way, and adult's oral dose is 1-200mg/ day, and adult's injected dose is 1-50mg/ day.
When the present invention is used for preparation treatment antiarrhythmic medicament, can with Western medicine with antiarrhythmic effect or Chinese medicine coupling.
Little Thalictrum aquilegifolium L. var. sibiricum Regel aldin is treated ARR effect, embodies by following test:
Test example, little Thalictrum aquilegifolium L. var. sibiricum Regel aldin are to the influence of experimental arrhythmia animal
1, material
1.1 the little Thalictrum aquilegifolium L. var. sibiricum Regel aldin of medicine (from the herb of the high eyebrow Thalictrum aquilegifolium L. var. sibiricum Regel of ranunculaceae plant Thalictrum omeiense W.T.Wang et S.H.Wang, extracting); Chloroform (Nanjing chemical reagent two factories); Epinephrine (Shanxi Tai Sheng pharmaceutical Co. Ltd); Barium chloride (biology is built up in Nanjing); Aconitine, U.S. sigma company; Mexiletine hydrochloride (Shanghai medicine Group Co.,Ltd), urethane (Shanghai chemical reagent packing factory).
1.2 the animal Kunming mouse, body weight 30.0 ± 2.0g; The big ear rabbit of Japan, body weight 2.8 ± 0.5Kg; The Wistar rat, body weight 300 ± 20g.Provide by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center.
1.3 instrument biological function experimental system BL-420E (Chengdu TME Technology Co., Ltd.).
2, the date processing measurement data with
A t check is organized in expression.The numeration data is carried out x
2(2 * 2) check.
3, test method
3.1 chloroform is brought out the effect of quivering in the mice chamber
Get mice, male and female half and half are divided into 5 groups at random, and 10 every group, wherein the normal saline group is irritated stomach with the respective amount normal saline.High dose group, middle dosage group, low dose group irritate respectively that stomach gives 6.4,3.2, the little Thalictrum aquilegifolium L. var. sibiricum Regel aldin of 1.6mg/Kg; Positive controls is irritated stomach and is given mexiletine hydrochloride 32.0mg/Kg.Successive administration 7 days, 1 time/day, behind the last administration 30min, each Mus is put into the bell glass that contains 2ml chloroform cotton balls 500ml respectively, when treating that mouse breathing is about to stop, cuing open breast immediately and observe the chamber of the appearance number of mice of quivering, and occurrence rate quivers to calculate respectively the chamber of group.
3.2 epinephrine is brought out the effect of rabbit arrhythmia
Get rabbit, male and female half and half are divided into 5 groups at random, and 6 every group, wherein the normal saline group is irritated stomach with the respective amount normal saline.High dose group, middle dosage group, low dose group irritate respectively that stomach gives 1.6,0.8, the little Thalictrum aquilegifolium L. var. sibiricum Regel aldin of 0.4mg/Kg; Positive controls is irritated stomach and is given mexiletine hydrochloride 8.0mg/Kg.Successive administration 7 days, 1 time/day, behind the last administration 30min, inject urethane 1.2mg/Kg anesthesia respectively, write down each rabbit front II with electrocardiograph and lead behind the ECG, intravenous injection epinephrine 40 μ g/Kg, 4S has injected, and observes the rhythm of the heart, synchronous recording ECG by showing the glass device, till when extremely recovering sinus rhythm fully, calculate arrhythmia time of origin and persistent period.
3.3 anti-barium chloride brings out the rat ventricular effect
Get rat male and female half and half, be divided into 5 groups at random, 10 every group, wherein the normal saline group is irritated stomach with the respective amount normal saline.High dose group, middle dosage group, low dose group irritate respectively that stomach gives 3.2,1.6, the little Thalictrum aquilegifolium L. var. sibiricum Regel aldin of 0.8mg/Kg; Positive controls is irritated stomach and is given mexiletine hydrochloride 16.0mg/Kg.Successive administration 7 days, 1 time/day, behind the last administration 30min, inject urethane 1.2mg/Kg anesthesia respectively, write down each rabbit front II with electrocardiograph and lead behind the ECG, intravenous injection barium chloride 4mg/Kg, 4S has injected, and observes the rhythm of the heart, synchronous recording ECG by showing the glass device, till when extremely recovering sinus rhythm fully, calculate arrhythmia time of origin and persistent period.
3.4 anti-aconitine brings out the rat ventricular effect
Get rat male and female half and half, random packet, 12 every group, wherein the normal saline group is irritated stomach with the respective amount normal saline.High dose group, middle dosage group, low dose group irritate respectively that stomach gives 3.2,1.6, the little Thalictrum aquilegifolium L. var. sibiricum Regel aldin of 0.8mg/Kg; Positive controls is irritated stomach and is given mexiletine hydrochloride 1.6 * 10
-2G/Kg.Successive administration 7 days, 1 time/day, behind the last administration 30min, inject urethane 1.2mg/Kg anesthesia respectively, write down each rabbit front II with electrocardiograph and lead behind the ECG,, calculate arrhythmia time of origin and 1 hour survival rate through sublingual vein constant speed injection aconitine 0.09 μ g/min.
4, result of the test
4.1 chloroform is brought out the influence of quivering in the mice chamber
Result of the test sees Table 1, and the result shows, compares with the normal saline group, and the mice number that quivers in positive controls, each dosage group chamber of appearance of little Thalictrum aquilegifolium L. var. sibiricum Regel aldin obviously reduces, and occurrence rate obviously reduces (P＜0.05,0.01).
Table 1 pair chloroform brings out the influence (n=15) of quivering the mice chamber
Compare with the normal saline group, * P＜0.05, * * P＜0.01, down together
4.2 epinephrine is brought out the ARR influence of rabbit
Result of the test sees Table 2, the result shows, compare with the normal saline group, positive controls, each dosage group of little Thalictrum aquilegifolium L. var. sibiricum Regel aldin can significantly be postponed epinephrine and be brought out the ARR time of origin of rabbit (P＜0.01), shorten the ARR persistent period (P＜0.05,0.01).
Table 2 pair epinephrine bring out the ARR influence of rabbit (x ± S, n=6)
| Group | Dosage (mg/Kg) | Time of origin (S) | Persistent period (S) |
| The normal saline group | - | 12.3±2.2 | 215.9±54.3 |
| Mexiletine hydrochloride | 8.0 | 25.4±3.4** | 93.1±39.7** |
| Low dose group | 0.4 | 15.8±2.8* | 149.6±40.0* |
| Middle dosage group | 0.8 | 20.1±3.0** | 114.8±47.2** |
| High dose group | 1.6 | 24.3±3.1** | 106.7±39.1** |
4.3 barium chloride is brought out the influence of rat ventricular
Result of the test sees Table 3, the result shows, compare with the normal saline group, positive controls, each dosage group of little Thalictrum aquilegifolium L. var. sibiricum Regel aldin can significantly be postponed the time of origin (P＜0.01) that barium chloride brings out rat ventricular, shorten the ARR persistent period (P＜0.05,0.01).
Table 3 pair barium chloride brings out the influence of rat ventricular
| Group | Dosage (mg/Kg) | Time of origin (S) | Persistent period (min) |
| The normal saline group | - | 2.5±1.1 | 33.5±8.1 |
| Mexiletine hydrochloride | 16.0 | 16.6±2.0** | 17.6±7.9** |
| Low dose group | 0.8 | 5.4±1.7** | 24.3±6.6* |
| Middle dosage group | 1.6 | 9.8±2.0** | 20.5±6.1** |
| High dose group | 3.2 | 13.6±1.6** | 18.6±7.0** |
4.4 aconitine is brought out the influence of rat ventricular
Result of the test sees Table 4, the result shows, compare with the normal saline group, positive controls, each dosage group of little Thalictrum aquilegifolium L. var. sibiricum Regel aldin can significantly be postponed the time of origin (P＜0.05,0.01) that aconitine brings out rat ventricular, improve 1 hour survival rate (P＜0.05,0.01) that aconitine brings out the arrhythmia rat.
Table 4 pair aconitine brings out the influence (n=12) of rat ventricular
| Group | Dosage (mg/Kg) | Time of origin (min) | 1h survival rate (%) |
| The normal saline group | - | 24.3±7.9 | 16.7 |
| Mexiletine hydrochloride | 16.0 | 45.7±8.8** | 83.3** |
| Low dose group | 0.8 | 32.0±8.3* | 58.3* |
| Middle dosage group | 1.6 | 37.5±9.0** | 75.0** |
| High dose group | 3.2 | 41.0±8.7** | 83.3** |
In sum, little Thalictrum aquilegifolium L. var. sibiricum Regel aldin can obviously resist chloroform and bring out mice, epinephrine and bring out that rabbit, barium chloride are brought out rat, aconitine brings out rat ventricular, and above-mentioned effect is that it treats ARR pharmacological basis.
The specific embodiment
Embodiment 1
Tablet: little Thalictrum aquilegifolium L. var. sibiricum Regel aldin 10g, starch 190g granulates, and tabletting is made 1000.Instructions of taking: be grown up one time 1,2 times on the one.
Embodiment 2
Capsule: little Thalictrum aquilegifolium L. var. sibiricum Regel aldin 10g, starch 190g, mixing is made 1000.Instructions of taking: be grown up one time 1,2 times on the one.
Claims (1)
1. little Thalictrum aquilegifolium L. var. sibiricum Regel aldin is as the application of unique active component in preparation treatment antiarrhythmic medicament.
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| CN2009102329879A CN101919854B (en) | 2009-10-20 | 2009-10-20 | Application of thaliadine in preparing medicament for treating arrhythmia |
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| CN101919854A CN101919854A (en) | 2010-12-22 |
| CN101919854B true CN101919854B (en) | 2011-11-09 |
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2009
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Non-Patent Citations (4)
| Title |
|---|
| Liao WT，et al.alkaloids of thalictrum XXVII. new hypotensive aporphine-benzylisoquinoline derived dimeric alkaloids from thalictrum minus race B.《Lloydia》.1978,第41卷(第3期),271-276. * |
| 南京中医药大学.倒水莲.《中药大辞典(下册)》.上海科学技术出版社,2006,(第2版),2637页. * |
| 李诒光等.唐松草属植物的化学与药理研究概况.《江西中医学院学报》.2001,第13卷(第2期),93-95. * |
| 程绍瑜等.峨嵋唐松草碱抗实验性心律失常作用.《中国药理学通报》.1988,第4卷(第4期),237-240. * |
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Address after: 400711 North Hot Springs Street, Beibei District, Chongqing City, Chongqing photoelectric instrument City Industrial Park Patentee after: Chongqing gifted biotechnology Limited by Share Ltd Address before: 400711 North Hot Springs Street, Beibei District, Chongqing City, Chongqing photoelectric instrument City Industrial Park Patentee before: UNIBIO BIOLOGICAL TECHNOLOGY CO., LTD. |