CN102293929B - Chinese medicine composition for treating arrhythmia and preparation method thereof - Google Patents
Chinese medicine composition for treating arrhythmia and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a Chinese medicine composition for treating arrhythmia and a preparation method thereof. The Chinese medicine composition disclosed by the invention comprises bulk drugs such as ginseng fruit, coptis chinensis, ginseng fruit total saponin extract and coptis total alkaloid extract, the Chinese medicine composition disclosed by the invention can effectively resist arrhythmia caused by electrosimulation on the heart of a rabbit, the arrhythmia of a rat caused by aconitine and the arrhythmia caused by coronary artery ligation, effective refractive period (ERP) can be obviously prolonged, ventricular fibrillated threshold (VFT) can be improved, frequency of ventricular premature (VP) and the frequency of ventricular tachycardia (VT) can be reduced, action potential amplitude (APA) and rate of rise of the action potential (Vmax) of a papillary muscle cell of a ventricle of a cavy can be obviously reduced, and the ERP and action potential duration (APD) are obviously improved, thus the Chinese medicine composition is effective for treating the arrhythmia.
Description
Invention field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of ARR pharmaceutical composition and preparation method thereof for the treatment of.
Background technology
Arrhythmia (Cardiac Arrhythmia) refers to frequency, the rhythm and pace of moving things, origin position, conduction velocity and exciting order unusual of cardiac impulse.Normal heart excitement originates from the sinuatrial node of heart, and sinuatrial node is the highest " headquarter " of cardiac pacing.Pass to down successively atrium and ventricle with the time in sequence by " instruction " that " headquarter " sends, excite the corresponding position of heart to produce excited.
Arrhythmia is common clinical, frequently-occurring disease, and serious arrhythmia is one of final cause of the death of the patients such as myocardial hypertrophy, myocardial ischemia, myocardial infarction and heart failure.In recent years, the non-medicine mode of doctor trained in Western medicine is treated arrhythmia and has been obtained great progress, such as radio-frequency catheter ablation radical cure atrioventricular nodal reentrant tachycardia, A-V reentry tachycardia, atrial flutter and ventricular tachycardia; Embedded automatic cardiac cardioverter defibrillators (ICD) can significantly be improved the prognosis of malignant arrhythmia.But the uncertain therapeutic efficacy of the radio-frequency catheter ablation of atrial fibrillation is cut, and the radio-frequency catheter ablation success rate of malignant ventricular arrhythmia is low, even or accepted ICD treatment and also need Long-term taking medicine.Therefore, antiarrhythmic drug remains the ARR main method for the treatment of.Yet, arrhythmia Western medicine preparation ubiquity causes (urging) Arrhythmia, and the toxicity such as negative inotropic's property, internal organs toxic action, especially large-scale epidemiology test---arrhythmia inhibition test (CAST) is the result show, ventricular premature contraction and non-standing chamber speed with patient behind the I class antiarrhythmic drug treatment myocardial infarction, not only can not improve patient's prognosis, significantly increase on the contrary patient's sudden death and case fatality rate.Therefore, select suitable antiarrhythmic drug most important for the control of this disease.
The Chinese medicine arrhythmia has some superiority at aspects such as relief of symptoms and the quality of making the life better, has shown the applications well prospect.Arrhythmia belongs to the category of the traditional Chinese medical science " cardiopalmus ", " palpitation with a distress feeling ".Chinese medicine thinks, many, the internal damage by the excessive seven emotions deficient owing to the internal organs negative and positive of qi and blood of cardiopalmus, qi depression to blood stasis reciprocal action cause become homeless foster, heart arteries and veins mistake of the heart and freely cause.Most traditional Chinese medical science scholars think, cardiopalmus belongs to the card of deficiency in origin and excess in superficiality, and morbidity is, healthy energy virtual loss (deficiency in origin) weak by plain body, and evil poison is taken advantage of a weak point (mark is real), invade and heart arteries and veins due to.Select suitable Chinese patent medicine by typing is dialectical, for improve above-mentioned symptom, the control state of an illness has preferably curative effect.
We are according to for many years scientific research and a large amount of clinical treatment experience, start with from the etiology and pathogenesis of primary disease, established the Therapeutic Method of QI invigorating detoxifcation, treat clinically and obtained good curative effect in the various arrhythmia processes: Radix Ginseng and Rhizoma Coptidis are applied to Chinese medical discrimination among the patient of " cardiopalmus " deficiency of vital energy ecchymosis for the Chinese medicine compound of the monarch and his subjects' medicine, treatment through about continuous 2 weeks, the symptoms such as arrhythmia all can access good improvement.
According to the QI invigorating antidotal therapy principle of the above-mentioned traditional Chinese medical science " cardiopalmus ", the present invention in the formulation optimization process, in multiple QI invigorating Chinese medicine (comprising Radix Ginseng, Radix Panacis Quinquefolii and the Radix Astragali etc.), preferred ginseng fruit saponins; In multiple heat and toxic materials clearing away medicine (comprising Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri and Fructus Gardeniae etc.), preferred Rhizoma Coptidis total alkaloids.Can not reduce on the drug action basis of original medical material, improve the utilization rate to existing Chinese crude drug, alleviate the present situation of scarcity of resources, can also greatly reduce the cost of new drug development simultaneously.
The science of the composition of the ARR Chinese medicine composition for the treatment of provided by the invention has obtained the proof of chemistry and modern Chinese medicine pharmaceutical technology.Chemistry and modern Chinese medicine pharmaceutical technology show: Herba Herminii has blood pressure lowering, blood sugar lowering, the pharmacological actions such as arrhythmia and the reperfusion injury that resists myocardial ischemia.Wherein, ginseng fruit saponins (Ginsengfruirsaponins, GFS) is the main effectively active component of Herba Herminii, claims again ground sperm saponin, is the Ginsenosides material that extracts from the mature fruit of Araliaceae Radix Ginseng.Now studies have shown that: this Ginsenosides material contains the multiple saponin components such as ginsenoside Re, Rb1, Rb2, Rc, Rg1 and Rd.To detection assay such as its physicochemical constant that carries out, ultraviolet, nuclear-magnetism, mass spectrums, to have confirmed its chemical constitution and found that ginsenoside Re's content is the highest in the ginseng fruit saponins, content reaches 85%, is 30 times of Radix Ginseng, accounts for 6% of full fruit.Substitute Radix Ginseng with ginseng fruit saponins and be used as medicine, can on the basis that does not reduce the Radix Ginseng drug action, improve the utilization rate to existing ginseng crude drug, alleviate the present situation of ginseng resource's scarcity, can also greatly reduce the cost of new drug development simultaneously.
Chemistry and modern Chinese medicine pharmaceutical technology show: contain Rhizoma Coptidis total alkaloids in the Rhizoma Coptidis dry rhizome.Rhizoma Coptidis total alkaloids is the main effectively active component that extracts in the ranunculaceae plant Rhizoma Coptidis dry rhizome.Now studies have shown that: this Rhizoma Coptidis total alkaloids contains berberine, coptisine, 13-methyl-.psi.-coptisine., palmatine, jateorhizine, epiberberine and magnoflorine etc.Rhizoma Coptidis total alkaloids has significant heart failure resistance, arrhythmia, cholesterol reducing, anti-vascular smooth muscle cell proliferation processed, improves the effects such as insulin resistant, antiplatelet, antiinflammatory; Wherein, the antiarrhythmic effect is particularly remarkable.Studies show that in a large number, Rhizoma Coptidis total alkaloids can by pharmacological actions such as over reach current potential time-histories and effective refractory period, inhibition sodium channel, inhibition flow of calcium ions and free radical resisting damages, can suppress various arrhythmia, eliminate and turn back.Be used as medicine with the total alkaloids extract in the Rhizoma Coptidis, can effectively improve the drug action of Rhizoma Coptidis, reach the purpose of discarding the dross and selecting the essential.
Summary of the invention
The object of the invention is to disclose a kind of ARR pharmaceutical composition for the treatment of, another object of the present invention is to disclose the preparation method of this pharmaceutical composition.
The present invention seeks to be achieved by the following scheme:
The crude drug of pharmaceutical composition of the present invention consists of:
Herba Herminii 8-30 weight portion Rhizoma Coptidis 1 weight portion;
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Herba Herminii 12 weight portion Rhizoma Coptidis 1 weight portion;
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Herba Herminii 25 weight portion Rhizoma Coptidis 1 weight portion.
The crude drug of pharmaceutical composition of the present invention consists of:
Ginseng fruit saponins extract 0.8-4 weight portion coptis total alkaloid extract 1 weight portion;
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Ginseng fruit saponins extract 1.2 weight portion coptis total alkaloid extracts 1 weight portion;
Or
Ginseng fruit saponins extract 2 weight portion coptis total alkaloid extracts 1 weight portion;
Or
Ginseng fruit saponins extract 3 weight portion coptis total alkaloid extracts 1 weight portion;
Or
Ginseng fruit saponins extract 1.8 weight portion coptis total alkaloid extracts 1 weight portion.
The preparation method of pharmaceutical composition of the present invention is:
The preparation method of ginseng fruit saponins extract: suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 0.5-1.5 times of weight after, stirred 5-15 minute, and left standstill Cryoprecipitation 2-4h, draw supernatant, the metal screen coarse filtration, filtrate imports in the receiver; Remaining pulp extracts 2 times: add 0.5-1.5 times of weight purified water heating extraction 1-3h for the first time, add for the second time 0.5-1.5 times of weight purified water heating extraction 1-3h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 1-4L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, again upper prop absorption, then wash from bottom to up resin to colourless with purified water, use again the ethanol of 70-90%V/V from top to bottom, flow velocity 3.5-6.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract;
The preparation method of coptis total alkaloid extract is: after Rhizoma Coptidis is pulverized, get an amount of Rhizoma Coptidis powder, the ethanol that adds 8-12 times of weight 60-80%V/V, reflux, extract, 2-5 time, each 0.5-2.5h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 3-8%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 1-3BV/h, behind the purified water eluting with 2-5BV, with the ethanol elution of the 40-60%V/V of 3-8BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract.
The preparation method of pharmaceutical composition of the present invention is preferably:
The preparation method of ginseng fruit saponins extract: suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1 times of weight after, stirred 10 minutes, leave standstill, Cryoprecipitation 3h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1 times of weight purified water heating extraction 2h for the first time, add for the second time 1 times of weight purified water heating extraction 1.5h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 2-3L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, again upper prop absorption, then wash from bottom to up resin to colourless with purified water, use again the ethanol of 80%V/V from top to bottom, flow velocity 5.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract.See Fig. 1.
The preparation method of coptis total alkaloid extract: after Rhizoma Coptidis is pulverized, get an amount of Rhizoma Coptidis powder, the ethanol that adds 10 times of weight 70%V/V, reflux, extract, 3 times, each 1h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 5%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 2BV/h, behind the purified water eluting with 3BV, with the ethanol elution of the 50%V/V of 5BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract.See Fig. 2.
Wherein said Herba Herminii is the ripe dry fruit of Araliaceae Radix Ginseng; Described Rhizoma Coptidis is ranunculaceae plant Rhizoma Coptidis dry rhizome.
Wherein the ginseng fruit saponins extract adopts ginsenoside Re (C in the Radix Ginseng by HPLC fruit total saponin extract preferably with reference to Chinese Pharmacopoeia version (First appendix VID) in 2005 method
48H
82O
18) content must not be less than 6-10%, with reference to Chinese Pharmacopoeia version (First appendix VA) in 2005 method, adopt ultraviolet visible spectrophotometry, the content of measuring total saponins in the ginseng fruit saponins extract take the ginsenoside Re as reference substance is 70-90%; Ginsenoside Re (C in preferably ginseng's fruit total saponin extract
48H
82O
18) content must not be less than 8.0%, the content of total saponins is 82% in the ginseng fruit saponins extract.
Wherein coptis total alkaloid extract is preferably with reference to " the 2005th edition (First appendix VA) method of Chinese pharmacopoeia, adopting the content of the total alkaloids in the determined by ultraviolet spectrophotometry coptis total alkaloid extract is 40-60%, and the content of the total alkaloids in the preferred coptis total alkaloid extract is 50%.
Get the above-mentioned raw materials medicine, behind the mix homogeneously, add conventional adjuvant, make clinically acceptable granule, tablet, capsule, pill, slow releasing preparation, oral liquid or injection etc. according to common process.
The proportion of pharmaceutical composition of the present invention is with ginsenoside Re (C in the ginseng fruit saponins extract
48H
82O
18), the content of the total alkaloids in total saponins and the coptis total alkaloid extract contained different extraction ratios for the basis, when extraction ratio was high, the crude drug of input was just few, extraction ratio is low, then the input of corresponding increase crude drug.
The pharmacological results shows, the ARR Chinese medicine composition for the treatment of provided by the invention, can effectively resist the arrhythmia that the electricity irritation Rabbit Heart brings out, the dog arrhythmia that the rat ventricular of Aconitine Induced and coronary artery ligation cause, can significantly prolong effective refractory period (ERP), improve ventricular fibrillation threshholds (VFT), reduce ventricular premature contraction (VP) number of times and ventricular tachycardia (VT) number of times, can make Guinea-pig Papillary Muscles action potentials of cells amplitude (APA) and action potential climbing speed
(Vmax) significantly reduce, effective refractory period (ERP) and action potential duration (APD) significantly increase, and are treatment arrhythmia (names of disease of tcm: effective Chinese medicine composition cardiopalmus).
Description of drawings
Fig. 1 is the extraction and purification process flow chart of ginseng fruit saponins extract.
Fig. 2 is the extraction and purification process flow chart of coptis total alkaloid extract.
Following experimental example and embodiment all for the explanation but be not limited to the present invention.
Experimental example 1 compositions is on the impact (experiment in vitro) of guinea-pig heart chamber papillary muscles action potentials of cells
1.1 experimental technique
(1) laboratory animal and grouping: 30 of 300g-400g Cavia porcelluss (Institute of Genetics, Academia Sinica's animal center provides), male and female are not limit.Animal is divided into 3 groups at random: (compositions is prepared by embodiment 1 method for Normal group (giving normal saline), hypoxic-ischemic group (giving normal saline), hypoxic-ischemic+compositions group, give the compositions by adult's dosage conversion post dose), every group 8, fed continuously 10 days.
(2) medication: Normal group, rush with 95% (V/V) O with the Locke liquid of improveing
2With 5% (V/V) CO
2Constant temperature, constant speed perfusion.The hypoxic-ischemic group, perfusate simulation anoxia composition (mmol/l), NaCL 134.3, and KCL 5.4, CaCl
21.8, MgCl
20.5, NaHCO
3, NaH
2PO
40.9, sodium lactate 20.2, and in ischemia liquid, pass to 95% (V/V) O
2With 5% (V/V) CO
2The saturated gas perfusion, (PO
2About 5kPa) hypoxic-ischemic+compositions group, in the hypoxic-ischemic perfusate, add compositions.
(3) record of Guinea-pig Papillary Muscles cell separation and action potential: hit unconsciously and open breast, take out rapidly heart, place 95% (V/V) O of 37 ℃
2With 5% (V/V) CO
2In the saturated tyrode's solution, isolate papillary muscles, be fixed in constant temperature (36 ± 0.5) ℃, constant current (5mlmon
-1) the perfusion trench bottom.With for handling instrument bipolar stainless steel electrode being inserted cell, treat to demonstrate on the amplifier current potential-70～-90mV is resting potential, is 1.5 times stimulation of threshold value through the wide 1ms of stimulus isolator output wave, intensity with stimulator then, frequency is 1Hz.Recording electrode is for filling with 3mmolL
-1The glass electrode of Kcl, resistance is 10-15M Ω, draws action potential after the insertion, signal in the input double beam oscillograph, in BL420S biological function experimental system input computer, is analyzed with the professional software routine processes after microelectrode amplifier amplifies simultaneously.
(4) observation index: effective refractory period (ERP), action potential duration (APD), action potential amplitude (APA) and action potential climbing speed (Vmax).
1.2. statistical method
Adopt SPSS13.0 software to carry out statistical analysis, all data mean ± standard deviation
Expression, relatively with the t check, P＜0.05 is thought statistical significance between group.
1.3 experimental result
See Table 1.Compare with the hypoxic-ischemic group, hypoxic-ischemic+compositions group can make ventricular muscle cell APA, Vmax significantly reduce (P＜0.05), makes ERP and APD significantly increase (P＜0.05).
Table 1 compositions is on the impact of guinea-pig heart chamber papillary muscles action potentials of cells
Annotate: compare * P＜0.05 with the hypoxic-ischemic group.
The arrhythmia experimentation that experimental example 2 combination treatment electricity irritation Rabbit Hearts bring out (experiment in the body)
1.1 test method
(1) laboratory animal and grouping
42 of cleaning level new zealand rabbits, male and female are regardless of, body weight 2.5 ± 0.25kg, be divided at random 4 groups: Normal group (giving normal saline), model control group, positive drug control group (giving atlansil), compositions group (giving the compositions by the preparation of embodiment 1 method), every group 8, fed continuously 10 days.
(2) ventricular fibrillation threshholds determination experiment:
Free diet, drinking-water during the administration are to administration fasting in the 9th day.30min after the last administration, with pentobarbital sodium 30mg/kg intravenous anesthesia, dorsal position is fixed, and in the inboard subcutaneous electrode needle of assigning of rabbit extremity, traces synchronously 3 and leads electrocardiogram; The neck and chest preserved skin, tracheal intubation, connect the expiration machine, insert bipolar conduit through right common carotid artery, put the electrode tip of conduit and adjust electrode in the aorta initial part, until occur satisfied H ripple on the image, the record His bundle electrogram, the quadrupole conduit of another root is inserted right atrium by right external jugular vein, the conduit die opening is 2mm, and extremely wide is 1mm, external diameter 1.5mm, with its a pair of electrode pace-making atrium, to the electrode recording right atrial signal of telecommunication, and judge the position of electrode with the waveform of this signal with another, pacing electrode is in right ventricle top, after finishing the atrium programmed electrical stimulation, be badly in need of pushing conduit to right ventricle, record V ripple, more capable ventricle programmed electrical stimulation, current intensity is 2 times of relaxing period threshold values, pulsewidth 2ms.
(3) index determining:
Relaxing period threshold of excitation (DET): adopt the S1S2 method to measure.Adopt (the wide 2ms of ripple, wave spacing 148ms, intensity 1mA) to drive heart, 100ms applies a S2 behind the 8th S1 stimulates (the wide 2ms of ripple), and initial strength 0.1mA increases progressively with 0.1mA first, accurate with 0.02mA again, take the minimum stimulation intensity that can cause the ventricle excitement as DET.
Effective refractory period (ERP): adopt the S1S2 method, S1 arranges ditto, progressively moves forward at diastasis period (100ms) with the S2 of 2 times of DET intensity, measure with the 10ms step-length first, accurate with the 2ms step-length again, until S2 can not cause the ventricle excitement, the S1 of this moment, the S2 interval, be ERP.
Ventricular fibrillation threshholds (VFT) is measured: adopt train, the wide 5ms of ripple, wave spacing 5ms, umber of pulse 10.Stimulate to provide adopt the R ripple to trigger, per 25 heartbeats trigger once and stimulate, and increase progressively 0.5mA at every turn, quiver the minimum stimulation intensity of (〉=6 irregular chamber property ripples) as ventricular fibrillation threshholds take the firm chamber of bringing out.
1.2 statistical method
Adopt SPSS13.0 software to carry out statistical analysis, all data mean ± standard deviation
Expression, relatively with the t check, P＜0.05 is thought statistical significance between group
1.3 experimental result:
See Table 2.Behind the electricity irritation Rabbit Heart, bring out arrhythmia, compare with model control group, ERP and VFT obviously raise (P＜0.05) in positive group, compositions intervention group, compare not statistically significant with positive controls.
The ARR impact that table 2 compositions is brought out the electricity irritation Rabbit Heart
Annotate: compare * P＜0.05 with model control group.
The pharmacodynamic study of the rat ventricular effect of the anti-Aconitine Induced of experimental example 3 compositionss (experiment in the body)
1.1 test method
(1) laboratory animal and grouping
30 of healthy cleaning level SD rats, body weight 180 ± 20g, male.(Institute of Genetics, Academia Sinica's animal center provides) is divided into 3 groups at random, 10 every group.The 1st group is model group, gives normal saline; The 2nd group is test group, gives the compositions by the preparation of embodiment 1 method; The 3rd group of positive matched group gives atlansil.
(2) foundation of the rat ventricular model of Aconitine Induced: the above gavage volume of respectively organizing is 20mlkg
-1Then 30min gastric infusion before the test gives respectively respectively to organize rats by intraperitoneal injection pentobarbital sodium (30mgkg
-1) anesthesia, be fixed in operating-table, separate left jugular vein intubate input medicine, tail vein insert head sword-shaped needle input aconitine.As the II electrocardiographic recording that leads.With morning moving pump from the tail vein with 5 μ gkg
-1Min
-1Constant speed is injected aconitine, until heart beating stops, monitoring electrocardio therebetween and changes.
(3) index determining: the aconitine consumption when recording room premature beat (VP), ventricular tachycardia (VT), chamber property fibrillation (VF) and cardiac arrest (CA).
1.2 statistical method: adopt SPSS13.0 software to carry out statistical analysis, all data mean ± standard deviation
Expression, relatively with the t check, P＜0.05 is thought statistical significance between group.
1.3 experimental result:
See Table 3.Compare with model control group, aconitine consumption when the ventricular premature contraction of compositions and positive controls (VP), ventricular tachycardia (VT), chamber property fibrillation (VF) and cardiac arrest (CA) all obviously increases (P＜0.05), positive controls is compared with model control group, not statistically significant.
Table 3 compositions on the impact of the rat ventricular of Aconitine Induced (
μ g)
Annotate: compare * P＜0.05 with model control group
The anti-coronary artery ligation of experimental example 4 compositionss causes the pharmacodynamic study of dog Arrhythmia
1.1 experimental technique
(1) laboratory animal and grouping: healthy beasle dog, 24, be divided at random 4 groups (n=6), the 1st group is Normal group, gives normal saline; The 2nd group is model control group, gives normal saline; The 3rd group of positive medicine matched group, gavage gives atlansil; The 4th group is test medication group, gives the compositions by the preparation of embodiment 1 method.
(2) coronary artery ligation causes the foundation of dog arrhythmia model: give lumbar injection pentobarbital sodium 30mgkg during experiment
-1Operating-table is fixed in anesthesia, and tracheotomy in patients is made tracheal intubation connection respirator and carried out artificial ventilation; Make left neck artery, jugular vein and separate, the monitoring of action arteries and veins intubate, recording blood pressure, the row jugular vein intubate normal saline (per minute 8-10 drips) that slowly instils keeps vein unobstructed, in order to administration; Fixedly ECG electrode in animal foot with the monitoring, the recording ecg situation; After recording respectively the 5min normal ECG, open breast in left breast the 4th intercostal space, expose heart, cause myocardial ischemia to change in ramus descendens anterior arteriae coronariae sinistrae 1/2 place ligation.When treating that changing appears in electrocardiogram, record 5min electrocardiogram result then give respectively normal saline, atlansil or compositions by above-mentioned grouping and dosage, and electrocardiogram changes after the record administration.
(3) index determining: add up respectively ventricular premature contraction (VP) number of times, ventricular tachycardia (VT) number of times that occur in administration front and back heart rate, the every 5min, counting chamber premature beat percentage rate, ventricular tachycardia percentage rate.
1.2 statistical method
Adopt SPSS13.0 software to carry out statistical analysis, all data mean ± standard deviation
Expression, and with the difference between t check analysis group innerlich anwenden front and back and matched group and administration group, P＜0.05 is thought statistical significance.
1.3 experimental result:
See Table 4.After coronary artery ligation causes the dog arrhythmia, give after the different disposal, compare with model control group, positive controls and compositions intervention group all can obviously reduce ventricular premature contraction (VP) percentage rate and ventricular tachycardia (VT) percentage rate (P＜0.05).
Table 4 compositions on coronary artery ligation cause the ARR impact of dog (
μ g, n=10)
Annotate: compare * P＜0.05 with Normal group
The preparation of experimental example 5 pharmaceutical composition crude drug of the present invention and collaborative experiment
1. sample and dosage
(1) ginseng fruit saponins extract and coptis total alkaloid extract composition sample
It is an amount of to be in mass ratio that 1.2: 1 ratio is got the mixture of the ginseng fruit saponins extract (total saponin content is 82%) of embodiment 1 preparation and coptis total alkaloid extract (total alkaloid content is 50%), give rat by 120mg/kg dosage gavage, observe drug action.
(2) ginseng fruit saponins extract sample
The ginseng fruit saponins extract (total saponin content is 82%) of getting embodiment 1 preparation is an amount of, gives rat by 120mg/kg dosage gavage, observes drug action.
(3) coptis total alkaloid extract sample
The coptis total alkaloid extract (total alkaloid content is 50%) of getting embodiment 1 preparation is an amount of, gives rat by 120mg/kg dosage gavage, observes drug action.
2. drug action research
Adopt rat that the drug action of pharmaceutical composition of the present invention and its crude drug is compared.Pharmacological experimental method and result are as follows:
40 of healthy SD rats, body weight 160g～280g is divided into model group (giving normal saline), positive drug group (giving atlansil), pharmaceutical composition group of the present invention, Herba Herminii saponin's extract group and coptis total alkaloid extract group (n=8 only).After giving corresponding medicine 14d, fasting water 8h.The anesthesia of intravenous injection 1.2g/kg urethane.Dorsal position is fixed, expose femoral vein, put remaining needle, adopt Biological Signal Collecting System record standard limbs II lead electrocardiogram, corresponding grouping intravenous injection aconitine 30L/kg has annotated observation index in the 5s: ventricular premature contraction (VPB), ventricular tachycardia (VT), the frequency of ventricular fibrillation (VF) and the persistent period of single.Arrhythmia point system: Score=(log10VPBs)+2 (log10number of episodes of VT)+2[(log10number of episodesof VF)+(log10 total duration of VF)], be used for the arrhythmia order of severity is carried out quantitative analysis.
Table 5 drug effect comparative result
Annotate: compare * P＜0.05, * * P＜0.01 with model group.
The experimental result explanation, the drug action of pharmaceutical composition group of the present invention obviously is better than ginseng fruit saponins extract or the independent medication group of coptis total alkaloid extract.
The proportioning screening experiment of experimental example 6 pharmaceutical preparatioies of the present invention
Combination principle according to traditional Chinese medical science supplementing QI and nourishing YIN clearing away heat method treatment cardiopalmus, mark as investigating index take the arrhythmia of rat, ginseng fruit saponins extract and coptis total alkaloid extract have been compared with 0.6: 1,1.2: 1,1.8: 1 and 2.4: 1 the ratio compositions of mixing (compositions is prepared by embodiment 1 method, the mass ratio that is equivalent to respectively ginseng fruit saponins extract effective ingredient and coptis total alkaloid extract effective ingredient is 1: 1,2: 1,3: 1 and 4: 1) drug action, mark as investigating index take the arrhythmia of rat, the drug action of more variant ratio extract, experimental technique is the same.The results are shown in Table 6.
The drug effect diversity ratio of the ginseng fruit saponins of table 6 different proportion and Rhizoma Coptidis total alkaloids
Annotate: compare * P＜0.05, * * P＜0.01 with model group
The experimental result explanation, the optimal proportion of ginseng fruit saponins and Rhizoma Coptidis total alkaloids is 2: 1 (mass ratio that is equivalent to ginseng fruit saponins extract and coptis total alkaloid extract is 1.2: 1).
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1: capsule
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1 times of weight after, stirred 10 minutes, leave standstill, Cryoprecipitation 3h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1 times of weight purified water heating extraction 2h for the first time, add for the second time 1 times of weight purified water heating extraction 1.5h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 2-3L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, then again upper prop absorption wash resin to colourless from bottom to up with purified water, use again the ethanol of 80%V/V from top to bottom, flow velocity 5.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved.
Wherein the ginseng fruit saponins extract adopts ginsenoside Re (C in the Radix Ginseng by HPLC fruit total saponin extract with reference to Chinese Pharmacopoeia version (First appendix VID) in 2005 method
48H
82O
18) content must not be less than 8.0%; With reference to Chinese Pharmacopoeia version (First appendix VA) in 2005 method, adopt ultraviolet visible spectrophotometry, the content of measuring total saponins in the ginseng fruit saponins extract take the ginsenoside Re as reference substance is 82%.
Rhizoma Coptidis is got an amount of Rhizoma Coptidis powder after pulverizing, and adds the ethanol of 10 times of weight 70%V/V, reflux, extract, 3 times, each 1h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 5%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 2BV/h, behind the purified water eluting with 3BV, with the ethanol elution of the 50%V/V of 5BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved.
Wherein coptis total alkaloid extract is with reference to " the 2005th edition (First appendix VA) method of Chinese pharmacopoeia, adopting the content of the total alkaloids in the determined by ultraviolet spectrophotometry coptis total alkaloid extract is 50%.
Get ginseng fruit saponins extract 40g and coptis total alkaloid extract 20g, fully behind the mixing, add conventional adjuvant, be prepared into capsule according to common process, every capsules 0.25g approximately contains ginseng fruit saponins 20mg, Rhizoma Coptidis total alkaloids 10mg, Coming-of-Age Day consumption: 2 tablets/times, 3 times/days.Taboo: avoid with Oletum Trogopterori, Rhizoma et radix veratri (Radix Rhizoma Veratri) with clothes.
Embodiment 2: tablet
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1.5 times of weight after, stirred 8 minutes, leave standstill, Cryoprecipitation 2.5h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1.3 times of weight purified water heating extraction 2.5h for the first time, add for the second time 0.8 times of weight purified water heating extraction 1.2h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 3-4L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, then again upper prop absorption wash resin to colourless from bottom to up with purified water, use again the ethanol of 85%V/V from top to bottom, flow velocity 4L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved.
Wherein the ginseng fruit saponins extract adopts ginsenoside Re (C in the Radix Ginseng by HPLC fruit total saponin with reference to Chinese Pharmacopoeia version (First appendix VID) in 2005 method
48H
82O
18) content must not be less than 7.0%; With reference to Chinese Pharmacopoeia version (First appendix VA) in 2005 method, adopt ultraviolet visible spectrophotometry, the content of measuring total saponins in the ginseng fruit saponins extract take the ginsenoside Re as reference substance is 86%.
Rhizoma Coptidis is got an amount of Rhizoma Coptidis powder after pulverizing, and adds the ethanol of 11 times of weight 65%V/V, reflux, extract, 3 times, each 2h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 6%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 1.5BV/h, behind the purified water eluting with 2.5BV, with the ethanol elution of the 55%V/V of 4BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved.
Wherein coptis total alkaloid extract is with reference to " the 2005th edition (First appendix VA) method of Chinese pharmacopoeia, adopting the content of the total alkaloids in the determined by ultraviolet spectrophotometry coptis total alkaloid extract is 56%.
Get ginseng fruit saponins extract 24.4g and coptis total alkaloid extract 20g, fully behind the mixing, add conventional adjuvant, be prepared into tablet according to common process.
Embodiment 3: pill
Get ginseng fruit saponins extract 18g and the coptis total alkaloid extract 20g of embodiment 1 preparation, fully behind the mixing, add conventional adjuvant, be prepared into pill according to common process.
Embodiment 4: oral liquid
The ratio that is in mass ratio 1.8: 1 is got ginseng fruit saponins extract and coptis total alkaloid extract, fully behind the mixing, adds conventional adjuvant, is prepared into oral liquid according to common process, wherein ginsenoside Re (C in the ginseng fruit saponins extract
48H
82O
18) content must not be less than 6.0%, the content of total saponins is 88%, the content of the total alkaloids in the coptis total alkaloid extract is 50%.
Embodiment 5: granule
The ratio that is in mass ratio 4: 1 is got ginseng fruit saponins extract and coptis total alkaloid extract, fully behind the mixing, adds conventional adjuvant, is prepared into granule according to common process, wherein ginsenoside Re (C in the ginseng fruit saponins extract
48H
82O
18) content must not be less than 9.0%, the content of total saponins is 75%, the content of the total alkaloids in the coptis total alkaloid extract is 45%.
Embodiment 6: drop pill
The ratio that is in mass ratio 3: 1 is got ginseng fruit saponins extract and coptis total alkaloid extract, fully behind the mixing, adds conventional adjuvant, is prepared into granule according to common process, wherein ginsenoside Re (C in the ginseng fruit saponins extract
48H
82O
18) content must not be less than 10%, the content of total saponins is 80%, the content of the total alkaloids in the coptis total alkaloid extract is 42%.
Embodiment 7: tablet
Herba Herminii 12kg Rhizoma Coptidis 1kg
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1 times of weight after, stirred 10 minutes, leave standstill, Cryoprecipitation 3h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1 times of weight purified water heating extraction 2h for the first time, add for the second time 1 times of weight purified water heating extraction 1.5h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 2-3L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, then again upper prop absorption wash resin to colourless from bottom to up with purified water, use again the ethanol of 80%V/V from top to bottom, flow velocity 5.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved;
Rhizoma Coptidis is got an amount of Rhizoma Coptidis powder after pulverizing, and adds the ethanol of 10 times of weight 70%V/V, reflux, extract, 3 times, each 1h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 5%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 2BV/h, behind the purified water eluting with 3BV, with the ethanol elution of the 50%V/V of 5BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved;
Get above-mentioned ginseng fruit saponins extract and coptis total alkaloid extract, fully behind the mixing, add conventional adjuvant, be prepared into tablet according to common process.
Embodiment 8: capsule
Herba Herminii 25kg Rhizoma Coptidis 1kg
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1.2 times of weight after, stirred 8 minutes, leave standstill, Cryoprecipitation 2.5h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1.3 times of weight purified water heating extraction 2.5h for the first time, add for the second time 0.8 times of weight purified water heating extraction 1.2h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 3-4L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, then again upper prop absorption wash resin to colourless from bottom to up with purified water, use again the ethanol of 85%V/V from top to bottom, flow velocity 4L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved;
Rhizoma Coptidis is got an amount of Rhizoma Coptidis powder after pulverizing, and adds the ethanol of 11 times of weight 65%V/V, reflux, extract, 3 times, each 2h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 6%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 1.5BV/h, behind the purified water eluting with 2.5BV, with the ethanol elution of the 55%V/V of 4BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract, after the sampling pack, fill in label and hang on the bag, after the assay was approved, sealing is preserved; Get ginseng fruit saponins extract and the coptis total alkaloid extract of above-mentioned preparation, fully behind the mixing, add conventional adjuvant, be prepared into capsule according to common process.
Embodiment 9: drop pill
Get Herba Herminii 25kg and Rhizoma Coptidis 1kg, according to common process, add conventional adjuvant, make drop pill.
Claims (16)
1. treat ARR pharmaceutical composition for one kind, it is characterized in that the crude drug of this pharmaceutical composition consists of:
Herba Herminii 8-30 weight portion Rhizoma Coptidis 1 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:
Herba Herminii 12 weight portion Rhizoma Coptidis 1 weight portion.
3. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:
Herba Herminii 25 weight portion Rhizoma Coptidis 1 weight portion.
4. treat ARR pharmaceutical composition for one kind, it is characterized in that the crude drug of this pharmaceutical composition consists of:
Ginseng fruit saponins extract 0.8-4 weight portion coptis total alkaloid extract 1 weight portion.
5. pharmaceutical composition as claimed in claim 4 is characterized in that the crude drug of this pharmaceutical composition consists of:
Ginseng fruit saponins extract 1.2 weight portion coptis total alkaloid extracts 1 weight portion.
6. pharmaceutical composition as claimed in claim 4 is characterized in that the crude drug of this pharmaceutical composition consists of:
Ginseng fruit saponins extract 2 weight portion coptis total alkaloid extracts 1 weight portion.
7. pharmaceutical composition as claimed in claim 4 is characterized in that the crude drug of this pharmaceutical composition consists of:
Ginseng fruit saponins extract 3 weight portion coptis total alkaloid extracts 1 weight portion.
8. pharmaceutical composition as claimed in claim 4 is characterized in that the crude drug of this pharmaceutical composition consists of:
Ginseng fruit saponins extract 1.8 weight portion coptis total alkaloid extracts 1 weight portion.
9. such as the arbitrary described pharmaceutical composition of claim 4-8, it is characterized in that the ginsenoside Re is C in the ginseng fruit saponins extract in this pharmaceutical composition
48H
82O
18Content must not be less than 6%, the content of total saponins is 70-90% in the ginseng fruit saponins extract, the content of the total alkaloids in the coptis total alkaloid extract is 40-60%.
10. pharmaceutical composition as claimed in claim 9 is characterized in that the ginsenoside Re is C in the ginseng fruit saponins extract in this pharmaceutical composition
48H
82O
18Content must not be less than 8.0%, the content of total saponins is 82% in the ginseng fruit saponins extract, the content of the total alkaloids in the coptis total alkaloid extract is 50%.
11. such as the preparation method of claim 1,2,3,4,5,6,7,8 or 10 arbitrary described pharmaceutical compositions, it is characterized in that the method comprises the steps:
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 0.5-1.5 times of weight after, stirred 5-15 minute, leave standstill, Cryoprecipitation 2-4h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 0.5-1.5 times of weight purified water heating extraction 1-3h for the first time, add for the second time 0.5-1.5 times of weight purified water heating extraction 1-3h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 1-4L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, again upper prop absorption, then wash from bottom to up resin to colourless with purified water, use again the ethanol of 70-90%V/V from top to bottom, flow velocity 3.5-6.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract;
After Rhizoma Coptidis is pulverized, get an amount of Rhizoma Coptidis powder, the ethanol that adds 8-12 times of weight 60-80%V/V, reflux, extract, 2-5 time, each 0.5-2.5h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 3-8%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 1-3BV/h, behind the purified water eluting with 2-5BV, with the ethanol elution of the 40-60%V/V of 3-8BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract.
12. the preparation method of pharmaceutical composition as claimed in claim 9 is characterized in that the method comprises the steps:
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 0.5-1.5 times of weight after, stirred 5-15 minute, leave standstill, Cryoprecipitation 2-4h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 0.5-1.5 times of weight purified water heating extraction 1-3h for the first time, add for the second time 0.5-1.5 times of weight purified water heating extraction 1-3h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 1-4L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, again upper prop absorption, then wash from bottom to up resin to colourless with purified water, use again the ethanol of 70-90%V/V from top to bottom, flow velocity 3.5-6.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract;
After Rhizoma Coptidis is pulverized, get an amount of Rhizoma Coptidis powder, the ethanol that adds 8-12 times of weight 60-80%V/V, reflux, extract, 2-5 time, each 0.5-2.5h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 3-8%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 1-3BV/h, behind the purified water eluting with 2-5BV, with the ethanol elution of the 40-60%V/V of 3-8BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract.
13. the preparation method of pharmaceutical composition as claimed in claim 11 is characterized in that the method comprises the steps:
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1 times of weight after, stirred 10 minutes, leave standstill, Cryoprecipitation 3h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1 times of weight purified water heating extraction 2h for the first time, add for the second time 1 times of weight purified water heating extraction 1.5h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 2-3L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, again upper prop absorption, then wash from bottom to up resin to colourless with purified water, use again the ethanol of 80%V/V from top to bottom, flow velocity 5.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract;
After Rhizoma Coptidis is pulverized, get an amount of Rhizoma Coptidis powder, the ethanol that adds 10 times of weight 70%V/V, reflux, extract, 3 times, each 1h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 5%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 2BV/h, behind the purified water eluting with 3BV, with the ethanol elution of the 50%V/V of 5BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract.
14. the preparation method of pharmaceutical composition as claimed in claim 12 is characterized in that the method comprises the steps:
Suck the Radix Ginseng pulp from Radix Ginseng pulp cellar for storing things an amount of, in the tank filling, add the purified water of 1 times of weight after, stirred 10 minutes, leave standstill, Cryoprecipitation 3h draws supernatant, the metal screen coarse filtration is in the filtrate importing receiver; Remaining pulp extracts 2 times: add 1 times of weight purified water heating extraction 2h for the first time, add for the second time 1 times of weight purified water heating extraction 1.5h, extracted twice liquid is through plate-and-frame filtration, filtrate and supernatant liquid filtering are to the laggard D101 macroporous resin column absorption of head tank fruit glycosides, flow velocity is 2-3L/min, taste by mouth and then to judge that resin column absorption is saturated when bitterness is arranged, after the D101 macroporous resin column is adsorbed full closing, with purified water pipeline and resin column herb liquid are all ejected and collect head tank, again upper prop absorption, then wash from bottom to up resin to colourless with purified water, use again the ethanol of 80%V/V from top to bottom, flow velocity 5.5L/min, eluting is collected eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, the spray-dried machine spray drying of concentrated solution gets the ginseng fruit saponins extract;
After Rhizoma Coptidis is pulverized, get an amount of Rhizoma Coptidis powder, the ethanol that adds 10 times of weight 70%V/V, reflux, extract, 3 times, each 1h filters, merging filtrate, 60 ℃ of lower concentrating under reduced pressure Recycled ethanols further are concentrated into 0.5g/ml, get Rhizoma Coptidis extract, get Rhizoma Coptidis extract an amount of, NaOH with 5%w/w transfers to pH5～6, is that 1: 1 ratio is advanced macroporous resin adsorption in crude drug and resin quality ratio, and flow velocity is 2BV/h, behind the purified water eluting with 3BV, with the ethanol elution of the 50%V/V of 5BV, collect eluent, eluent is imported in the vacuum concentration recycling can, Recycled ethanol is to nothing alcohol flavor, being concentrated into relative density at 60 ℃ of lower medicinal liquids is 1.10-1.13, and the spray-dried machine spray drying of concentrated solution obtains coptis total alkaloid extract.
15. such as claim 1,2,3,4,5,6,7, the application of 8 or 10 arbitrary described pharmaceutical compositions in the ARR medicine of preparation treatment.
16. the application of pharmaceutical composition as claimed in claim 9 in the ARR medicine of preparation treatment.
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| 心律失常中医证治研究进展;朱浩;《中国中医急症》;20080630;第17卷(第6期);828-829 * |
| 朱浩.心律失常中医证治研究进展.《中国中医急症》.2008,第17卷(第6期),828-829. |
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