CN1723912A - Medicinal composition contg. ginseng secondary glycosides, prepn. method and application thereof - Google Patents
Medicinal composition contg. ginseng secondary glycosides, prepn. method and application thereof Download PDFInfo
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Abstract
A hypopanaxin composition for treating cardialgia, myocardial ischema and hemorrhagic shock contains such active components as 20-(S)-Rg3, 20-(R)-Rg3, 20-(R)-Rg2, 20-(S)-Rg2, 20-(S)-Rh1 and 20-(R)-Rh1. It is prepared from the ginseng family of plants through extracting, acidolyzing and using macroreticulr resin to separate, purify and concentrate.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains Radix Ginseng effective site and its production and application, particularly relate to a kind of total secondary ginseng glucoside's pharmaceutical composition and its production and application.
Background technology
Radix Ginseng is the key medicine of traditional Chinese medical science QI invigorating.Nature and flavor with return through sweet, little hardship, flat.Function with cure mainly: strongly invigorating primordial QI, multiple arteries and veins takes off admittedly, invigorating the spleen to benefit the lung promotes the production of body fluid, and calms the nerves.Be used for weak body and prostration, the cold extremities faint pulse, insufficiency of the spleen lack of appetite, the deficiency of the lung is breathed with cough, and Tianjin wound is thirsty, and interior-heat is quenched one's thirst, and prolonged illness is empty wins, palpitation with fear insomnia, sexual impotence cold womb; Heart failure, cardiogenic shock.
The traditional Chinese medical science and the combination of Chinese and Western medicine are clinical to be confirmed; Radix Ginseng and preparation thereof have pharmacologically actives such as the myocardial contraction of enhancing, coronary artery dilator, coronary blood flow increasing, minimizing myocardial oxygen consumption, protection reperfusion injury of cardiac muscle, anticoagulant, antithrombase, and clinical practice is in treatment of diseases such as obstruction of qi in the chest and cardialgia (coronary heart disease), arteriosclerosis.
The cause of disease of obstruction of qi in the chest and cardialgia mainly be " weakened YANG QI is not transported in the heart, for a long time then the yin subjugating yang position and be numbness knot " (" Lei Zheng Zhi Cai a ● thoracic obstruction piece of writing "), " or because of experiencing the cold-evil; mouthful cold thing of food; in have hot and suffocatingly, have the dead blood of pertinacious phlegm, or form chest pain because of the angry stagnation of QI " (seeing " doctor's mirror at all times ● pained ").
After people in middle age, body constitution descends, the five internal organs degradation, and visceral dysfunction, plain body YANG QI deficiency is attacked by pathogen such as cold and summer-heat again, or eating and drinking without temperance, and have a liking for the food delicious food, or ponder over overstrain, or disorder of emotion and cause obstruction of qi in the chest and cardialgia.Its sick position is at the heart, and it is all dirty to relate to lung, spleen, liver, kidney.Pathological change is the imbalance of internal organs negative and positive of qi and blood, deficiency of heart-blood, and flaccidity of the heart-yang causes stagnating heart meridians such as the stagnation of QI, cold coagulation, expectorant are turbid, blood stasis, causes blockage of the cardiac vessels, qi depression to blood stasis and falling ill.Pathogenesis is a deficiency in origin and excess in superficiality, and deficiency in origin is that the motive, painstaking effort, the heart-yin are lost void or deficiency of heart-YANG and kidney-YANG; Mark is real to be that the stagnation of QI, cold coagulation, expectorant are turbid, blood stasis resistance numbness heart arteries and veins etc., and deficiency in origin aggravates disease with the real often reciprocal causation of mark in the pathogenic process, presents simulataneous insufficiency and excessive, specimen with existing complicated syndrome.The rule of treatment is a rule of treatment with YIN and YANG balance regulating, temperature compensation yang-energy, promoting flow of QI and blood.Qi being the governor of blood, gas promoting the circulation of blood are then gone.The QI invigorating sun that shakes, blood circulation promoting and blood stasis dispelling are the important rules of treatment obstruction of qi in the chest and cardialgia.
Modern scientific research is the result show: the main bioactive ingredients of Radix Ginseng is the ginsenoside.Though Radix Ginseng Rubra and Radix Ginseng are contained saponin, its saponin monomer is different, contains the saponin that does not have in the Radix Ginseng in the Radix Ginseng Rubra---ginsenoside Rg2, Rg3, Rh1, Rh2 etc.These new saponin are in the Radix Ginseng course of processing, through steaming, when dry, the secondary saponin that ginsenoside's hydrolysis produces.
These secondary saponin have many new activity, for example: ginsenoside Rh1, Rh2, Rg3 have tangible active anticancer, and cancerous cell is induced differentiation again, but inducing cancer cell is divided into healthy cell again, other saponin monomer does not but have this effect, perhaps action intensity a little less than.The ginsenoside Rg3 has stronger inhibitory action to collagen or the inductive platelet aggregation of ADP.Ginsenoside Rh1 is converted into fibrin to the Fibrinogen of thrombin induction the obvious suppression effect.
In addition, in recent years use the result of serum pharmacological theory research ginsenoside's internal metabolism to show, former Radix Ginseng saponin is human body internal absorption factor very low (ginsenoside Rb1 is oral only to absorb 1%), and the active ingredient that really is absorbed by the body is the secondary saponin that produces through the Enterobacter cloaca metabolism.The Wang Benxiang professor finds that behind the oral ginsenoside Rg1, the biological activity that is absorbed into blood mainly is the secondary saponin Rh1 that produces through the Enterobacter cloaca metabolism when research ginsenoside internal metabolism process.
The Yan Yongqing professor is in the active ingredient process of research SHENGMAI YIN, find the common good effect of frying in shallow oil than single medicinal material branch that decocts of SHENGMAI YIN compound recipe, after the common decoction of compound recipe, the ginsenoside in the soup mainly is the secondary saponin Rg2 of Radix Ginseng, Rg3, Rh1, and former Radix Ginseng saponin disappears.This result of study shows that the main biological activity of compound recipe SHENGMAI YIN is ginsenoside Rg2, Rg3, Rh1.
But these saponin natural content are extremely low, and for example: the content of Rg3 in Radix Ginseng is 0.0003% only, and the content in Radix Ginseng Rubra is about 0.03%, and Rh2 and C-K do not exist in natural ginseng, only contain Rh2 about 0.001% in Radix Ginseng Rubra.And C-K is ginsenoside's an intestinal metabolite.The secondary saponin compound of these Radix Ginsengs is owing to obtain difficulty, and essential feather weight amount almost is impossible to carry out drug development.Therefore, it is significant to adopt new method to prepare above-claimed cpd.
Summary of the invention
One of purpose of the present invention is to overcome the former Radix Ginseng saponin shortcoming that absorption rate is very low in human body, biological activity is more weak, and a kind of total secondary ginseng glucoside's pharmaceutical composition is provided.The secondary saponin of Radix Ginseng is an active stronger effective ingredient in the Radix Ginseng, and the content of the secondary saponin of active component Radix Ginseng is extremely low in the natural ginseng.
One of the present invention is total secondary ginseng glucoside's pharmaceutical composition, is achieved through the following channels.
The present invention is a kind of total secondary ginseng glucoside's pharmaceutical composition, it is characterized in that:
Described total secondary ginseng glucoside's pharmaceutical composition comprises component: be the ginsenoside of aglycon with the former glycol of Radix Ginseng 1.: comprise the ginsenoside Rg3, the ginsenoside Rh2; 2. be the ginsenoside of aglycon with the former triol of Radix Ginseng: comprise ginsenoside Rg2, ginsenoside Rh1, the ginsenoside Rh 3, ginsenoside Rf, arasaponin R2;
By weight percentage, with the former glycol of Radix Ginseng, the former triol of Radix Ginseng be aglycon the ginsenoside's and more than 20%.
Wherein: the ginsenoside Rg3 is ginsenoside 20-(S)-Rg3 and/or ginsenoside 20-(R)-Rg3; Ginsenoside Rg2 is ginsenoside 20-(S)-Rg2 and/or ginsenoside 20-(R)-Rg2; Ginsenoside Rh1 is ginsenoside Rh1 20-(S)-Rh1 and/or ginsenoside 20-(R)-Rh1;
By weight percentage:
Rg3 is 10-30%, preferred 12-20%;
Rg2 is 1-20%, preferred 4-16%;
Rh1 is 1-10%, preferred 3-5%.
By weight percentage, with the former glycol of Radix Ginseng, the former triol of Radix Ginseng be aglycon the ginsenoside's and more than 50%.
The described plant that is used to extract total secondary ginseng glucoside's pharmaceutical composition is the araliaceae ginseng plant; They are various Radix Ginsengs, Radix Panacis Quinquefolii, Radix Notoginseng, Rhizoma Panacis Japonici, and wherein preferred plant is the Leptoradix Ginseng.
The extraction preparation method of described total secondary ginseng glucoside's pharmaceutical composition comprises hydrolysing step; As hydrolyst, preferred acetic acid is as hydrolyst with mineral acid or organic acid for described hydrolysing step.
In concrete enforcement, described pharmaceutical composition can contain total secondary ginseng glucoside extract, Radix Notoginseng total glucoside extract, additive, excipient and the medically acceptable carrier for the treatment of effective dose.
Total secondary ginseng glucoside's pharmaceutical composition of the present invention be Radix Ginseng extract through the weak acid hydrolysis, extract the total secondary saponin of preparation.Its main component source of students is closed: ginsenoside Rg3's (secondary glycosides) that ginsenoside Rb class (primary glycosides) hydrolysis produces, the ginsenoside Rg2 (secondary glycosides) that ginsenoside Re's class (primary glycosides) hydrolysis produces, and the ginsenoside Rh1 (secondary glycosides) of ginsenoside Rg1's class (primary glycosides) hydrolysis generation.Through the exploration of system, we have filtered out good high-pressure liquid phase condition of gradient elution, 20-of the present invention (S)-Rg3, and 20-(R)-Rg3,20-(S)-Rg2,20-(R)-Rg2,20-(S)-Rh1,20-(R)-Rh1 can reach good separating effect.
Two of purpose of the present invention provides a kind of total secondary ginseng glucoside's preparation of drug combination method.
Total secondary ginseng glucoside's preparation of drug combination method of two of the present invention is to realize like this.
Total secondary ginseng glucoside's preparation of drug combination method of the present invention comprises the steps:
(1) Radix Ginseng total saponins extracting solution preparation: with panax species, water or organic solvent extraction concentrate extracting solution again;
(2) hydrolyzed solution preparation: with mineral acid or organic acid is the above-mentioned concentrated extracting solution of catalyst hydrolysis,
(3) resin absorption: hydrolyzed solution passes through macroporous resin inspiration row attached column,
(4) remove impurity: the adsorption column that has absorbed hydrolyzed solution is removed impurity through water elution, aqueous alkali eluting, concentration at the ethanol elution below 35% again;
(5) eluting, concentrated, dry: use concentration at the ethanol elution adsorption column more than 35% after removing impurity, collect the ethanol elution more than 35%, be condensed into fluid extract, vacuum drying gets total secondary ginseng glucoside's pharmaceutical composition.
Catalyst in the described step (2) is selected from glacial acetic acid, propanoic acid, hydrochloric acid, sulphuric acid.Described hydrolysis carries out under 80-100 ℃ of condition, and described hydrolysis time is 3-8 hour; Preferred glacial acetic acid hydrolysis carries out under 99 ℃ of conditions, and hydrolysis time is 5 hours.
The macroporous resin of described step in 3. is the phenylethylene macroporous resin, comprises phenylethylene macroporous resin, ethyl styrene class macroporous resin, methyl styrene class macroporous resin.
The aqueous alkali of described step in 4. is by being selected from the aqueous solution that sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate are made into, and concentration is 0.1%-5.0%.Preferred sodium hydroxide is 0.3-0.7%, potassium hydroxide 0.4-0.8%, sodium carbonate or potassium carbonate 0.6-1.5%.Eluting is removed concentration of alcohol that impurity uses below 35%, preferred 15-25%.
Described step 5. in, the concentration of alcohol of eluting adsorption column is more than 35%, preferred 60-80%.
Three of purpose of the present invention provides the application of a kind of total secondary ginseng glucoside's pharmaceutical composition in the following medicine of preparation:
At preparation treatment flaccidity of the heart-yang, a little less than the insufficiency of heart-QI, the application in the medicine of the obstruction of qi in the chest and cardialgia that qi depression to blood stasis causes;
Application in the medicine of preparation treatment myocardial ischemia;
Application in the medicine of preparation treatment hemorrhagic shock;
Application in the medicine of preparation treatment heart failure.
The acute toxicity test of total secondary ginseng glucoside's pharmaceutical composition, total secondary ginseng glucoside's pharmaceutical composition mouse stomach administration maximum dosage-feeding is 7-15g/kg.
Total secondary ginseng glucoside's pharmaceutical composition is injected to mouse peritoneal, calculates LD through the Bliss method
50And 95% average fiducial limit scope is 0.19-0.25mg/kg.
2,13 weeks of SD rat repeat administration are recovered 4 all toxicity test results
With the total secondary ginseng glucoside respectively with 1500,750,250mg/kg gavages 13w for the SD rat continuously, detect behind the administration 13w and the generally variation of indexs such as situation, blood biochemical, hemogram, electrocardio, routine urinalysis, each organs and tissues pathology such as the weight of animals, appetite behind the drug withdrawal 4w, the result is as follows:
Total secondary ginseng glucoside's pharmaceutical composition is to the long-term continuous several times administration of Rodents rat, when being equivalent to 300 times of clinical plan consumptions, certain inhibitory action may be arranged the body weight gain of buck, may certain stimulation be arranged to immune system, male sexual organ and blood RBC, and make that blood BUN significantly raises, the GLU significance descends, the kidney metabolic function is produced certain toxic reaction, but do not see that obvious damage sexually transmitted disease (STD) reason changes, do not produce the organic lesion of internal organs, can recover no cumulative action after the drug withdrawal.Therefore can think, being equivalent to the administration below 150 times of clinical plan consumption, be safe dose to the Rodents rat.
Total secondary ginseng glucoside's pharmaceutical composition of the present invention cures mainly flaccidity of the heart-yang in preparation, a little less than the insufficiency of heart-QI, and the application in the new drug of the obstruction of qi in the chest and cardialgia that qi depression to blood stasis causes; And/or cure mainly application in the new drug of myocardial ischemia in preparation; And/or when preparation cures mainly application in the new drug of hemorrhagic shock, the dosage of total secondary ginseng glucoside's pharmaceutical composition, because of patient's state, body weight, administering mode etc. different different.Such as under non-oral situation, intramuscular, vein, enteral administration, being that aglycon and the former triol of Radix Ginseng are that the secondary saponin sum of various Radix Ginsengs of aglycon is calculated 0.02mg-200mg/kg. day at the extract more than 50% with the former glycol of Radix Ginseng, preferred 0.2mg-20mg/kg. day, be that aglycon and the former triol of Radix Ginseng are that the secondary saponin sum of various Radix Ginsengs of aglycon is calculated 0.1-4g/kg. day at the extract more than 50%, preferred 1-50mg/kg. day with the former glycol of Radix Ginseng under the oral situation.
This medicine is that the function according to Radix Ginseng cures mainly, actual efficacy in conjunction with modern Chinese medicine clinical practice Radix Ginseng treatment coronary heart disease, with reference to the latest developments of relevant Radix Ginseng pharmaceutical research both at home and abroad, from Radix Ginseng, extract the effective site-total secondary ginseng glucoside extract of preparation Radix Ginseng, development cure mainly flaccidity of the heart-yang, a little less than the insufficiency of heart-QI, the new drug of the obstruction of qi in the chest and cardialgia that qi depression to blood stasis causes.
Pharmacodynamic experiment of the present invention studies show that,
1. the total secondary ginseng glucoside extract has the remarkable effect that improves the dog acute myocardial ischemia, obviously alleviates by the degree of myocardial ischemia of epicardial electrogram mapping (∑-ST);
2. reduce through the shown infarct area of N-BT dyeing; Coronary flow in the time of can obviously increasing myocardial ischemia promotes that side Zhi Xunhuan is open and sets up the oxygen supply of increase cardiac muscle;
3. blood plasma 6-ketone-prostaglandin F in the time of can obviously raising myocardial ischemia
1a(6-Keto-PGF
1a) level and 6-Keto-PGF
1a/ TXB
2Ratio;
4. can significantly suppress the rat heart muscle ischemia that pituitrin causes;
5. can prevent and treat the myocardial ischemia that the rat coronary ligation causes by significance, its effect significantly is better than Radix Ginseng total saponins (P＜0.01);
6. the anti-cardiogenic shock effect of highly significant is arranged, to anesthetized dog shock model due to the ischemia, under the identical situation of dosage, total secondary ginseng glucoside about 20min after administration begins to play a role, and Radix Ginseng total saponins about 40min after administration begins to play a role, action effect a little less than; Generally speaking, the total secondary ginseng glucoside extract 20,30, the 40min time point, compare with Radix Ginseng total saponins, action effect has significant difference (P＜0.05 or P＜0.01), is being better than Radix Ginseng total saponins aspect speed of action and the action effect;
7. to BaCl
2Cause the animal model of rat ventricular, total secondary ginseng glucoside extract 200mg/kg can significantly delay the time (P＜0.05, P＜0.05) that VP, VT occur, significantly shorten the arrhythmia persistent period (P＜0.05), 100,50mg/kg can significantly shorten the arrhythmia persistent period (P＜0.05, P＜0.05);
8. total secondary ginseng glucoside extract 200mg/kg administration 7d in advance is to the inhibitory action that is formed with of test rat neck arteriovenous shut thrombosis;
9. the total secondary ginseng glucoside extract has inhibitory action to the platelet aggregation that ADP brings out, and especially high dose group has significant inhibitory effect to external platelet aggregation;
10. to the isolated rat heart ischemia-reperfusion, can improve coronary flow, improve heart beating strength within a certain period of time, and ischemic myocardium is had the certain protection ability.
Based on above traditional theory of Chinese medical science and tcm clinical practice experience and pharmacodynamic experiment scientific achievement, developed with the secondary saponin of Radix Ginseng is the flaccidity of the heart-yang that cures mainly of main effective ingredient, a little less than the insufficiency of heart-QI, the total secondary ginseng glucoside extract new drug of the obstruction of qi in the chest and cardialgia that qi depression to blood stasis causes.The patient takes and is developed into oral tablet and various other dosage form for convenience.
From the Leptoradix Ginseng, extract the effective site-total secondary ginseng glucoside extract of preparation Radix Ginseng, with each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 9.0%, 20-(R)-Rg3 is 9.0%, 20-(S)-Rg2 is 2.1%, 20-(R)-Rg2 is 2.1%, 20-(S)-Rh1 is 1.8%, and 20-(R)-Rh1 is 1.8%.
The concrete outcome of pharmacological experiment is as follows:
1, the total secondary ginseng glucoside extract is to the influence of dog to the dog myocardial ischemia
(1), the total secondary ginseng glucoside extract adopts ligation dog anterior descending coronary (LAD) to cause acute myocardial infarction model to the effect experiment of experimental dog acute myocardial infarction.With epicardial electrogram (EECG) mapping degree of myocardial ischemia (∑-ST) and myocardial ischemia scope (N-ST); Learn method (N-BT staining) with quantitative tissue and measure myocardial infarct size (MIS); Femoral vein is got blood thought-read flesh three enzymes: glutamic oxaloacetic transaminase, GOT (AST), creatine phosphokinase (CPK) and lactic acid dehydrogenase (LDH).Experimental result shows that the total secondary ginseng glucoside extract has the remarkable effect that improves the dog acute myocardial ischemia, obviously alleviates by the degree of myocardial ischemia of epicardial electrogram mapping (∑-ST); Reduce through the shown infarct of N-BT dyeing.Positive control drug DIAOXINXUE KANG, Radix Ginseng saponin and stem and leaf of Radix Ginseng saponin also show the identical effect that reduces myocardial infarction area.
(2), the total secondary ginseng glucoside extract rat heart muscle ischemia that adopts pituitrin to cause to the effect of rat heart muscle ischemia, observe the influence that medicine raises to the variation and the T ripple of ST section among the standard cardioelectric figure II.The result shows: compare with the blank group, total secondary ginseng glucoside extract 100-200mg/kg can significantly resist the variation of ST, the rising of T ripple (P＜0.05 or P＜0.01), its effect is relevant with dosage, shows that the total secondary ginseng glucoside extract can significantly suppress the rat heart muscle ischemia that pituitrin causes; Under equal experiment condition, Radix Ginseng total saponins 100mg/kg only shows and makes the T ripple raise degree to alleviate, but diltiazem 50mg/kg significance suppresses the variation (P＜0.05 or P＜0.01) of ST ripple, T ripple.
(3), the total secondary ginseng glucoside extract causes that to coronary ligation the influence of rat heart muscle ischemia is to rat coronary ligation model, successive administration 7d in advance, physical signs such as record electrocardio ECG II, heart rate, systolic pressure, diastolic pressure are put in the operation of execution coronary ligation in each observing time.The result shows, total secondary ginseng glucoside extract 100-200mg/kg all can suppress the variation (P＜0.01) that J is ordered by highly significant, and tangible dose-effect relationship is arranged, Ischemic Heart heart rate and blood pressure are not seen that significance influence (P＞0.05) is arranged, show and can prevent and treat the myocardial ischemia that coronary ligation causes by significance, its effect significantly is better than Radix Ginseng total saponins (P＜0.01).Under equal experiment condition, diltiazem 50mg/kg also can prevent and treat the myocardial ischemia effect that coronary ligation causes by significance, and selected Radix Ginseng total saponins 100mg/kg dosage, DIAOXINXUE KANG 100mg/kg dosage act on very not remarkable on this model.
2, the total secondary ginseng glucoside extract is to the influence of animal hemodynamics and myocardial oxygen consumption
The variation of every index of hemodynamics and myocardial oxygen consumption after the employing anesthetized open-chest dog observation administration.The result shows that after ligation anesthetized dog coronary artery formed myocardial ischemia, coronary flow had the short time compensatory to increase increasing degree about 10%.The visible coronary flow that obviously increases behind the total secondary ginseng glucoside extract medicine, the coronary flow in the time of can obviously increasing myocardial ischemia, promotion side Zhi Xunhuan opens and sets up, and increases the oxygen supply of cardiac muscle.15 ~ 180min coronary flow all has obvious rising behind three dosage group medicines, and the effect of 60min ~ 120min coronary blood flow increasing is the most remarkable, with before the medicine and the normal saline group relatively, notable difference (P＜0.01 and P＜0.001) is all arranged.The effect of remarkable increase Ischemic Heart coronary flow is arranged behind the positive control drug diltiazem medicine; DIAOXINXUE KANG also has the increase effect to the Ischemic Heart coronary flow, and increasing degree is about 10%; Radix Ginseng saponin and stem and leaf of Radix Ginseng saponin also increase coronary flow simultaneously.Blood plasma 6-ketone-prostaglandin F when the total secondary ginseng glucoside can obviously raise myocardial ischemia
1a(6-Keto-PGF
1a) level and 6-Keto-PGF
1a/ TXB
2Ratio.
3, the total secondary ginseng glucoside extract is to the influence of dog cardiogenic shock
Adopt anesthetized dog hemorrhagic shock model, each time point after administration is observed systolic arterial pressure (SBP) diastolic pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), maximum the rate of change (± dP/dt of left ventricular pressure
Max), physical signs such as heart rate.Select for use SHENMAI ZHUSHEYE to compare medicine, and compare with Radix Ginseng total saponins.The result shows, total secondary ginseng glucoside extract 100-200mg/kg systolic arterial pressure that hemorrhagic shock causes and diastolic pressure are descended significantly raise (P＜0.05), left ventricular systolic pressure and diastolic pressure remarkable rising (P＜0.05, P＜0.01), ± dP/dt
MaxAll significance raises (P＜0.05, P＜0.01), and comparatively obvious for the effect of left ventricle, low dosage 50mg/kg also shows remarkable effect, and obviously is better than Radix Ginseng total saponins 200mg/kg.Show that the total secondary ginseng glucoside has the anti-cardiogenic shock effect of highly significant.To anesthetized dog shock model due to the ischemia, under the identical situation of dosage, total secondary ginseng glucoside extract about 20min after administration begins to play a role, and Radix Ginseng total saponins about 40min after administration begins to play a role, action effect a little less than; Generally speaking, the total secondary ginseng glucoside 20,30, the 40min time point, compare with Radix Ginseng total saponins, action effect has significant difference (P＜0.05 or P＜0.01), thereafter time point, the action effect there was no significant difference, this illustrates that also the total secondary ginseng glucoside is better than Radix Ginseng total saponins at speed of action and action effect.
4, the total secondary ginseng glucoside is to BaCl
2Cause the influence of rat ventricular
Adopt rat sublingual vein injection BaCl
2Cause arrhythmia.Successive administration 7d in advance, implement modeling, putting physical signs such as record electrocardio ECG II, heart rate in each observing time, quivers (VF) incidence rate, arrhythmia persistent period in time and chamber that the time that observation and counting chamber premature beat (VP) occur, ventricular tachycardia (VT) occur.The result shows, total secondary ginseng glucoside 200mg/kg can significantly delay the time (P＜0.05, P＜0.05) that VP, VT occur, significantly shorten the arrhythmia persistent period (P＜0.05), 100,50mg/kg can significantly shorten the rule not normal persistent period (P＜0.05, P＜0.05); The positive control drug diltiazem not only significantly delays VP, VT time of occurrence (P＜0.01, P＜0.01), shortens the arrhythmia persistent period (P＜0.01), has also effectively suppressed VF incidence rate (P＜0.05); Selected Radix Ginseng total saponins 100mg/kg dosage, DIAOXINXUE KANG 100mg/kg dosage act on not remarkable on this model.
5, the total secondary ginseng glucoside is to the influence of thrombus in vivo formation
Total secondary ginseng glucoside 200mg/kg in advance administration 7d to the inhibitory action that is formed with of test rat neck arteriovenous shut thrombosis, as seen positive drug and tried thing and respectively organize thrombus weight and all be lower than matched group, relatively there were significant differences (P＜0.05) for positive drug diltiazem and matched group, relatively there were significant differences (P＜0.05) according to group to be tried object height dosage, along with the increase of drug dose, its thrombosis suppression ratio also increases.
6, the total secondary ginseng glucoside extract is to the influence of platelet aggregation
The total secondary ginseng glucoside extract has inhibitory action to the platelet aggregation that ADP brings out, and especially total secondary ginseng saponin high dose group has significant inhibitory effect to external platelet aggregation, suppression ratio even be higher than the aspirin positive controls.Adenyl cyclase on the excited platelet membrane of total secondary ginseng saponin energy is described, and suppresses the activity of phosphodiesterase, the cAMP level in the platelet is significantly improved, thereby can be good at suppressing hematoblastic gathering.
Compare comparison with Radix Ginseng total saponins, at the dosage of total secondary ginseng glucoside's dosage and Radix Ginseng total saponins identical or be lower than it in, the total secondary ginseng glucoside will obviously be better than the action effect of Radix Ginseng total saponins to the inhibitory action of platelet aggregation, even illustrate that the total secondary ginseng glucoside under the situation of smaller dose, also has inhibitory action to hematoblastic gathering.
7, the total secondary ginseng glucoside extract is to the influence of isolated heart ischemia-reperfusion
With total secondary ginseng glucoside extract 500mg/kg; Radix Ginseng total saponins 1000mg/kg; diltiazem 100mg/kg and DIAOXINXUE KANG 500mg/k dosage are given rat continuous oral administration 7d; the blood sampling separation of serum; the dilution of total secondary ginseng glucoside extract serum is a series of concentration groups; isolated rat heart is carried out perfusion; the result shows: total secondary ginseng glucoside extract high concentration group increases multiple filling 20min heart skip frame degree; irritate coronary flow increase in the 20-30min again; myocardium MDA content is significantly reduced; show that the active component of total secondary ginseng glucoside in serum can improve coronary flow; improve heart beating strength within a certain period of time, and ischemic myocardium is had the certain protection ability.Same effect is all arranged when Radix Ginseng total saponins, diltiazem, DIAOXINXUE KANG high concentration.There is not significant difference between the effect of total secondary ginseng glucoside extract 500mg/kg serum and Radix Ginseng total saponins 1000mg/kg serum.
8, general pharmacology research
For investigating the total secondary ginseng glucoside, carried out following research work to animal spirit nervous system, organism balance motion, with the synergism of spiritual nervous system medicine and to the influence of cardiovascular system, respiratory system etc.:
1, the total secondary ginseng glucoside extract is to the neural effect of spirit: to the active influence of mice general behavior; Influence to the mice autonomic activities; Influence to the motion of mice organism balance.
2, the synergism of total secondary ginseng glucoside extract and spiritual nervous system medicine: observe with the synergism of sleep threshold dose pentobarbital sodium; Observe with the synergism of pentobarbital sodium under the sleep threshold.
3, the total secondary ginseng glucoside extract is to the influence of cardiovascular system: to the influence of the blood pressure of Beagle dog, the rhythm of the heart, each ripple of electrocardio (ECG II).
4, the total secondary ginseng glucoside extract is to the influence of respiratory system: to the influence of the respiratory frequency of Beagle dog, degree of depth etc.
Experimental result shows: mice is oral 70,140, during 280mg/kg total secondary ginseng glucoside extract, mice general behavior, autonomic activities, balance exercise are not seen that the significance influence is arranged, oral 70,140,280mg/kg total secondary ginseng glucoside, do not see with sleep threshold dose (40mg/kg) and threshold under pentobarbital sodium (30mg/kg) generation synergism.Give the Beagle dog respectively oral total secondary ginseng glucoside extract 50,100,200mg/kg to respiratory frequency and the degree of depth, to systolic arterial pressure and diastolic pressure, to there are no significant the influence of electrocardio and heart rate.
Therefore can judge that the total secondary ginseng glucoside of oral pharmacodynamics dosage does not have obvious influence to respiratory system, the cardiovascular system of the animal spiritual nervous system of unifying, and does not have synergism with pentobarbital sodium class medicine.
9, safety evaluatio research
Carry out the chmice acute toxicity research, recovered 4 all toxicity tests in 13 weeks of SD rat repeat administration, 13 weeks of Beagle dog repeat administration recovered 4 all toxicity tests.
1, The acute toxicity tests
Total secondary ginseng glucoside extract mouse stomach administration maximum dosage-feeding is 8g/kg.
The total secondary ginseng glucoside extract is injected to mouse peritoneal, calculates LD through the Bliss method
50And 95% average fiducial limit scope is 0.246 ± 0.023mg/kg.
2,13 weeks of SD rat repeat administration are recovered 4 all toxicity test results
With the total secondary ginseng glucoside extract respectively with 1500,750,250mg/kg gavages 13w for the SD rat continuously, detect behind the administration 13w and the generally variation of indexs such as situation, blood biochemical, hemogram, electrocardio, routine urinalysis, each organs and tissues pathology such as the weight of animals, appetite behind the drug withdrawal 4w, the result is as follows:
The total secondary ginseng glucoside extract is to the long-term continuous several times administration of Rodents rat, when being equivalent to 300 times of clinical plan consumptions, certain inhibitory action may be arranged the body weight gain of buck, may certain stimulation be arranged to immune system, male sexual organ and blood RBC, and make that blood BUN significantly raises, the GLU significance descends, the kidney metabolic function is produced certain toxic reaction, but do not see that obvious damage sexually transmitted disease (STD) reason changes, do not produce the organic lesion of internal organs, can recover no cumulative action after the drug withdrawal.Therefore can think, being equivalent to the administration below 150 times of clinical plan consumption, be safe dose to the Rodents rat.
3,13 weeks of Beagle dog repeat administration are recovered 4 all toxicity test results
With the total secondary ginseng glucoside extract respectively in 900,450,210mg/kg is (with 60kg people 300mg every day, be equivalent to the clinical plan of people 180,90,42 times respectively) with dosage, gavage 13w continuously for the Beagle dog, detect behind the administration 13w and the generally variation of indexs such as situation, blood biochemical, hemogram, electrocardio, routine urinalysis, each organs and tissues pathology such as the weight of animals, appetite behind the drug withdrawal 4w, the result is as follows:
The total secondary ginseng glucoside extract is to the long-term continuous several times administration of non-Rodents Beagle dog, when being equivalent to 180 times of clinical plan consumptions, certain facilitation may be arranged the body weight gain of animal, make blood WBC that certain rising be arranged, since 6w, BUN in the serum, the rising of significance appears in ALP, to 13w, Crea in the serum, BUN, ALT, ALP, T-P significance all occurs and raises, and liver, kidney device coefficient has significance to raise, spleen heavily has trend of rising, and thymus heavily has a declining tendency, but there is no the difference of significance between group, pathological examination, two routine liver Mild edema are arranged, the visible atrophy of thymus gland of an example wherein, a routine kidney renal tubules kitchen range shape calcification.Result of the test shows, during 180 times of clinical plan consumptions, to liver, kidney, may produce certain toxicity damage.Can recover no cumulative toxicity behind the drug withdrawal 4w.
According to evaluation of test result, the total secondary ginseng glucoside is safe dose being equivalent to the administration below 90 times of clinical plan consumption to non-Rodents Beagle dog.
Total secondary ginseng glucoside's pharmaceutical composition of the present invention, as the instructions of taking of total secondary ginseng glucoside oral disintegration tablets:
The oral cavity buccal, one time 1～2.3 times on the one;
Points for attention:
1. under physician guidance, take by usage and dosage.
2. should not obey together with Rhizoma et radix veratri (Radix Rhizoma Veratri).
3. should not take during cat fever.
The specific embodiment
[embodiment 1]
Get Leptoradix Ginseng's root segment 10kg,, use the solvent of 5 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds isopyknic 99% glacial acetic acid, and hydrolysis is 5 hours under 97-99 ℃ of condition.Hydrolyzed solution adds isopyknic water, by D101 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 0.5% sodium hydroxide eluting, and water is eluted to neutral 20% ethanol elution of using, use 70% ethanol elution at last, collect 70% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.56kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 9.0%, and 20-(R)-Rg3 is 9.0%, and 20-(S)-Rg2 is 2.1%, and 20-(R)-Rg2 is 2.1%, and 20-(S)-Rh1 is 1.8%, and 20-(R)-Rh1 is 1.8%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 62%.
[embodiment 2]
Get Radix Ginseng decoction pieces 10kg,, use the solvent of 6 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds isopyknic 0.1% hydrochloric acid, and hydrolysis is 5 hours under 55-57 ℃ of condition.Hydrolyzed solution adds isopyknic water, by D2 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 1.5% sodium hydroxide eluting, and water is eluted to neutral 25% ethanol elution of using, use 70% ethanol elution at last, collect 70% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.35kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 8.8%, and 20-(R)-Rg3 is 8.8%, and 20-(S)-Rg2 is 2.2%, and 20-(R)-Rg2 is 2.2%, and 20-(S)-Rh1 is 1.8%, and 20-(R)-Rh1 is 1.8%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 58%.
[embodiment 3]
Get notoginseng decoction piece 10kg,, use the solvent of 5 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds isopyknic 99% glacial acetic acid, and hydrolysis is 5 hours under 97-99 ℃ of condition.Hydrolyzed solution adds isopyknic water, by DM2 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 3.5% sodium hydroxide eluting, and water is eluted to neutral 20% ethanol elution of using, use 75% ethanol elution at last, collect 75% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.38kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 5.7%, and 20-(R)-Rg3 is 5.7%, and 20-(S)-Rg2 is 7.3%, and 20-(R)-Rg2 is 7.3%, and 20-(S)-Rh1 is 2.2%, and 20-(R)-Rh1 is 2.2%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 65%.
[embodiment 4]
Get Stem and leaf of Radix Ginseng 10kg,, use the solvent of 5 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds isopyknic glacial acetic acid, and hydrolysis is 7 hours under 90-93 ℃ of condition.Hydrolyzed solution adds isopyknic water, by D101 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 1.2% sodium carbonate eluting, and water is eluted to neutral 30% ethanol elution of using, use 60% ethanol elution at last, collect 60% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.25kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 9.5%, and 20-(R)-Rg3 is 9.5%, and 20-(S)-Rg2 is 1.7%, and 20-(R)-Rg2 is 1.7%, and 20-(S)-Rh1 is 1.5%, and 20-(R)-Rh1 is 1.5%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 54%.
[embodiment 5]
Get Radix Panacis Quinquefolii decoction pieces 10kg,, use the solvent of 7 times of amounts, each 2.5 hours at every turn with 50% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds isopyknic glacial acetic acid, and hydrolysis is 5 hours under 97-99 ℃ of condition.Hydrolyzed solution adds isopyknic water, by DS2 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 0.8% potassium hydroxide eluting, and water is eluted to neutral 20% ethanol elution of using, use 80% ethanol elution at last, collect 80% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.35kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 11.0%, and 20-(R)-Rg3 is 11.0%, and 20-(S)-Rg2 is 0.9%, and 20-(R)-Rg2 is 0.9%, and 20-(S)-Rh1 is 1.2%, and 20-(R)-Rh1 is 1.2%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 57%.
[embodiment 6]
Get stem and leaf of Radix Notoginseng 10kg,, use the solvent of 5 times of amounts, each 4 hours at every turn with 60% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.0.5% sulphuric acid of weight such as concentrated solution adds, hydrolysis is 1 hour under 50-53 ℃ of condition.Hydrolyzed solution adds isopyknic water, by XAD-1 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 0.5% potassium hydroxide eluting, and water is eluted to neutral 15% ethanol elution of using, use 65% ethanol elution at last, collect 65% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.45kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 13.5%, and 20-(R)-Rg3 is 13.5%, and 20-(S)-Rg2 is 0.5%, and 20-(R)-Rg2 is 0.5%, and 20-(S)-Rh1 is 0.8%, and 20-(R)-Rh 1 is 0.8%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 63%.
[embodiment 7]
Get stem and leaf of Radix Panacis Quinquefolii 10kg,, use the solvent of 5 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds the propanoic acid of equivalent, and hydrolysis is 7 hours under 108-110 ℃ of condition.Hydrolyzed solution adds isopyknic water, by HP-30 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 5% potassium carbonate eluting, and water is eluted to neutral 35% ethanol elution of using, use 95% ethanol elution at last, collect 95% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.23kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 10.5%, and 20-(R)-Rg3 is 10.5%, and 20-(S)-Rg2 is 1.1%, and 20-(R)-Rg2 is 1.1%, and 20-(S)-Rh1 is 1.0%, and 20-(R)-Rh1 is 1.0%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 52%.
[embodiment 8]
Get Radix Ginseng decoction pieces 10kg,, use the solvent of 5 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds the propanoic acid of equivalent, and hydrolysis is 9 hours under 97-99 ℃ of condition.Hydrolyzed solution adds isopyknic water, by XAD-5 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 0.1% sodium hydroxide eluting, and water is eluted to neutral 35% ethanol elution of using, use 50% ethanol elution at last, collect 50% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.18kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 8.5%, and 20-(R)-Rg3 is 8.5%, and 20-(S)-Rg2 is 2.0%, and 20-(R)-Rg2 is 2.0%, and 20-(S)-Rh1 is 1.6%, and 20-(R)-Rh1 is 1.6%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 58%.
[embodiment 9]
Get Radix Ginseng Rubra decoction pieces 10kg,, use the solvent of 5 times of amounts, each 3 hours at every turn with 70% alcohol reflux 3 times.Merge extractive liquid,, concentrating under reduced pressure.Concentrated solution adds the glacial acetic acid of equivalent, and hydrolysis is 5 hours under 97-99 ℃ of condition.Hydrolyzed solution adds isopyknic water, by HP-10 type macroporous resin column.The complete back of last sample water is eluted to closely colourless, and is continuous with 0.3% sodium hydroxide eluting, and water is eluted to neutral 20% ethanol elution of using, use 70% ethanol elution at last, collect 70% ethanol elution, be evaporated to fluid extract, at 70 ℃ of vacuum dryings, get total secondary ginseng glucoside extract 0.25kg.With each content of effective of high-pressure liquid phase chromatogram therapy determining: 20-(S)-Rg3 is 8.8%, and 20-(R)-Rg3 is 8.8%, and 20-(S)-Rg2 is 2.2%, and 20-(R)-Rg2 is 2.2%, and 20-(S)-Rh1 is 1.9%, and 20-(R)-Rh1 is 1.9%.With ginsenoside 20-(R)-Rg3 is reference substance, and the content of measuring ginsenoside's total glycosides is 55%.
Claims (15)
1. total secondary ginseng glucoside's pharmaceutical composition is characterized in that described total secondary ginseng glucoside's pharmaceutical composition comprises following component:
1. be the ginsenoside of aglycon with the former glycol of Radix Ginseng, comprise the ginsenoside Rg3;
2. be the ginsenoside of aglycon with the former triol of Radix Ginseng, comprise ginsenoside Rg2 and ginsenoside Rh1;
By weight percentage, with the former glycol of Radix Ginseng, the former triol of Radix Ginseng be aglycon the ginsenoside's and more than 20%.
2. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 1 is characterized in that:
Wherein the ginsenoside Rg3 is ginsenoside 20-(S)-Rg3 and/or ginsenoside 20-(R)-Rg3; Ginsenoside Rg2 is ginsenoside 20-(S)-Rg2 and/or ginsenoside 20-(R)-Rg2; Ginsenoside Rh1 is ginsenoside Rh1 20-(S)-Rh1 and/or ginsenoside 20-(R)-Rh1;
By weight percentage: Rg3 is 10-30%, and Rg2 is 1-20%, and Rh1 is 1-10%.
3. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 2 is characterized in that:
By weight percentage, in described total secondary ginseng glucoside's pharmaceutical composition, Rg3 is 12-20%, and Rg2 is 4-16%, and Rh1 is 3-5%;
By weight percentage, with the former glycol of Radix Ginseng, the former triol of Radix Ginseng be aglycon the ginsenoside's and more than 50%.
4. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 1 is characterized in that:
The described plant that is used to prepare total secondary ginseng glucoside's pharmaceutical composition is a panax species.
5. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 4 is characterized in that:
The described plant that is used to extract total secondary ginseng glucoside's pharmaceutical composition is the Leptoradix Ginseng.
6. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 4 is characterized in that:
Described panax species is Radix Ginseng, Radix Panacis Quinquefolii, Radix Notoginseng or Rhizoma Panacis Japonici.
7. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 1 is characterized in that:
The extraction preparation method of described total secondary ginseng glucoside's pharmaceutical composition comprises hydrolysing step; Described hydrolysing step with mineral acid or organic acid as hydrolyst.
8. total secondary ginseng glucoside's pharmaceutical composition as claimed in claim 7 is characterized in that:
Described hydrolysing step uses acetic acid as hydrolyst.
9. as the described total secondary ginseng glucoside's pharmaceutical composition of one of claim 1～8, it is characterized in that:
Described pharmaceutical composition comprises total secondary ginseng glucoside extract, additive, excipient and the medically acceptable carrier for the treatment of effective dose.
10. as total secondary ginseng glucoside's preparation of drug combination method of one of claim 1～9, comprise the steps:
(1) Radix Ginseng total saponins extracting solution preparation: with panax species, water or organic solvent extraction concentrate extracting solution again;
(2) hydrolyzed solution preparation: with mineral acid or organic acid is the above-mentioned concentrated extracting solution of catalyst hydrolysis;
(3) resin absorption: hydrolyzed solution adsorbs by macroporous resin column;
(4) remove impurity: the adsorption column that has passed through hydrolyzed solution is removed impurity through water elution, aqueous alkali eluting, concentration at the ethanol elution below 35% again;
(5) eluting, concentrated, dry: use concentration at the ethanol elution adsorption column more than 35% after removing impurity, collect this ethanol elution, be condensed into fluid extract, vacuum drying gets total secondary ginseng glucoside's pharmaceutical composition.
11. the total secondary ginseng glucoside's preparation of drug combination method as claim 10 is characterized in that:
Catalyst in the described step (2) is selected from glacial acetic acid, propanoic acid, hydrochloric acid, sulphuric acid, and described hydrolysis carries out under 80-100 ℃ of condition, and described hydrolysis time is 3-8 hour.
12. the total secondary ginseng glucoside's preparation of drug combination method as claim 10 is characterized in that:
Catalyst in the described step (2) is a glacial acetic acid, and hydrolysis carries out under 99 ℃ of conditions, and hydrolysis time is 5 hours.
13. the total secondary ginseng glucoside's preparation of drug combination method as claim 10 is characterized in that:
Macroporous resin in the described step (3) is the phenylethylene macroporous resin, comprises phenylethylene macroporous resin, ethyl styrene class macroporous resin, methyl styrene class macroporous resin.
14. the total secondary ginseng glucoside's preparation of drug combination method as claim 10 is characterized in that:
Aqueous alkali in the described step (4) is selected from following material: the aqueous solution that sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate were made into, concentration are 0.1%-5.0%; It is 15-25% that eluting is removed the concentration of alcohol that impurity uses;
In the described step (5), the concentration of alcohol of eluting adsorption column is 60-80%.
15. the application of total secondary ginseng glucoside's pharmaceutical composition in the following medicine of preparation as one of claim 1～9:
At preparation treatment flaccidity of the heart-yang, a little less than the insufficiency of heart-QI, the application in the medicine of the obstruction of qi in the chest and cardialgia that qi depression to blood stasis causes;
Application in the medicine of preparation treatment myocardial ischemia;
Application in the medicine of preparation treatment hemorrhagic shock;
Application in the medicine of preparation treatment heart failure.
Priority Applications (10)
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| CNB2005100838556A CN100337636C (en) | 2005-07-14 | 2005-07-14 | Medicinal composition contg. ginseng secondary glycosides, prepn. method and application thereof |
| CA2614700A CA2614700C (en) | 2005-07-14 | 2006-07-05 | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
| ES06761360.4T ES2515891T3 (en) | 2005-07-14 | 2006-07-05 | Method of Preparation of a Pharmaceutical Composition Containing Ginseng Secondary Glycosides |
| JP2008520691A JP2009500432A (en) | 2005-07-14 | 2006-07-05 | Ginseng secondary glycoside pharmaceutical composition and its production method and application |
| US11/995,320 US7973014B2 (en) | 2005-07-14 | 2006-07-05 | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
| PCT/CN2006/001574 WO2007006208A1 (en) | 2005-07-14 | 2006-07-05 | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
| KR1020087003434A KR101182917B1 (en) | 2005-07-14 | 2006-07-05 | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
| EP06761360.4A EP1905444B1 (en) | 2005-07-14 | 2006-07-05 | Preparation method of a medicinal composition containing ginseng secondary glycosides |
| PL06761360T PL1905444T3 (en) | 2005-07-14 | 2006-07-05 | Preparation method of a medicinal composition containing ginseng secondary glycosides |
| HK08104922.7A HK1110520A1 (en) | 2005-07-14 | 2008-05-02 | Preparation method of a medicinal composition containing ginseng secondary glycosides |
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