CN100441589C - Puerarin compound containing water soluble group and its preparation and use - Google Patents

Puerarin compound containing water soluble group and its preparation and use Download PDF

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CN100441589C
CN100441589C CNB02159418XA CN02159418A CN100441589C CN 100441589 C CN100441589 C CN 100441589C CN B02159418X A CNB02159418X A CN B02159418XA CN 02159418 A CN02159418 A CN 02159418A CN 100441589 C CN100441589 C CN 100441589C
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puerarin
methyl
ylmethyl
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王林
王升启
李鲁
彭涛
丁雨
汪海
朱晓伟
金义光
徐娟
张首国
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Institute of Radiation Medicine of CAMMS
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Abstract

The present invention relates to a gegensu compound containing a watersoluble group, and salt used as medicine which are shown by a general formula I. R1, R2, R3 in the formula, a preparation method and a drug composition of a general formula I compound containing effective dose are shown in a text. The composition is used for treating or preventing cardiovascular and cerebrovascular diseases, particularly for treating various kinds of cardiovascular and cerebrovascular ischemia anoxia.

Description

The puerarin compound and method for making and the purposes that contain water-soluble group
Affiliated technical field
The present invention relates to puerarin compound that a class contains water-soluble group, can be used as medicinal salt, its preparation method, and the pharmaceutical composition that contains the compound of Formula I of effective dosage.Said composition is used for the treatment of or prevents cardiovascular and cerebrovascular diseases, particularly treats all kinds of cardiac-cerebral ischemia anoxias.
Figure C0215941800031
Background technology
Puerarin (Puerarin Pu Lelin, formula I, R 1=R 2=R 3=H) be effective constituent in the pulse family platymiscium root of kudzu vine, chemistry is by name 4 ', 7-dihydroxyl-8-β-D-glucose isoflavones, molecular weight is 416.For decades, people have done a large amount of work to the basis and the applied research of puerarin, prove that it truly has coronary artery dilator, improve myocardium shrinkage function, protection global ischemia cardiac muscle, and effect such as stimulate circulation.The clinical coronary heart disease that once was used for the treatment of, stenocardia, myocardial infarction, arteria retina and vein obstruction, diseases such as sudden deafness.Cardiovascular and cerebrovascular diseases is the dead primary cause of disease of China adult at present, as the new drug puerarin that improves cardiovascular and cerebrovascular circulation, since its novel structure, determined curative effect, thereby have important use value.
Prior art discloses puerarin and has the increase myocardial consumption of oxygen, and the vasodilation effect it is believed that it is that to have the beta adrenergic retardation relevant with it.Further investigation in recent years also finds to have multiple pharmacology new role in addition.Puerarin has stronger removing oxyradical and antioxygenation: under the normal circumstances, the generation and the removing of biological interior free yl are in the running balance, participate in sterilization, important physiological function such as substance metabolism, in case balance is destroyed, then can cause multiple disease such as inflammation, aging, shock, atherosclerosis, myocardial ischemia, calcium deficiency, medicine and alcoholism etc.Thereby can these diseases of enough antioxidant therapies.(modern combination of Chinese tradiational and Western medicine magazine such as Yuan Shikai's Tomb; 2000,9:2197-2199) research draws Pu Lelin and can effectively remove hyperpietic and the too much oxyradical of ischemic cerebral stroke patients, can strengthen the utilization ratio of cerebral tissue to glucose, high-energy phosphate bond is formed to be increased, the function of enzyme in splicing thread plastochondria and the tenuigenin promotes impaired brain tissue cell rehabilitation.Puerarin is also relevant with its antioxygenation to the provide protection that the mouse intestinal ischemia pours into liver injury again.
Prior art also discloses, puerarin can make the vaso-excitor material ET level of hypertension and functions in patients with unstable angina significantly descend, and vasodilator factor NO and plasma calcitonin gene related peptide level are significantly raise, and (neat magnificent pavilion Li Yue is identical, Chinese combination of Chinese tradiational and Western medicine magazine 200020 (9): 694-695).Its mechanism of action is: the 1. expansible coronary artery of puerarin, increase perfused tissue, and microcirculation improvement increases the oxygen-supplying amount of endotheliocyte, and metabolism improving alleviates damage; 2. puerarin makes oxyradical generate minimizing, and increases its clearance rate, alleviates the damage of radical pair endotheliocyte; 3. blood viscosity increases and can damage endothelium, and puerarin can reduce the blood degree, alleviates damage.After endothelial function improved, synthetic and release NO increased, and the synthetic of ET then reduces, and this may be one of mechanism of puerarin treatment coronary heart disease.
Prior art further discloses, and puerarin is for elevated platelet activation, nitric oxide synthetase, and hemorheology and cerebral blood flow all have stronger influence.The acting in conjunction of platelet activation and blood coagulation system is thrombotic basis.After using around the puerarin treatment UAP, the level of platelet membrane activated protein sign CD63, CD62P, fibrinolytic factor PAI-1 and inflammatory reaction thing C-RP all obviously descends, with relatively there were significant differences before the treatment (Liu Peixian etc., railway medical science 2000,28 (4): 237-238).NO produces by nitricoxide synthase (NOS), has proved that now NO has participated in the damage of cerebral ischemia reperfusion stream.NOS is divided into primary type (cNOS) and induces type (iNOS) two classes by function and characteristic.Rat experiment is the result show, puerarin has provide protection to the global brain ischemia reperfusion injury.Experimentation on animals shows that puerarin can improve retinal microcirculation, produces positive cooperativity with the coupling of hypotensive agents timolol, significantly improves the transmission of optic nerve axoplasm, plays the effect of protection optic nerve, also has the metabolic effect of the cerebral circulation of improvement and brain.Puerarin may also have neuroendocrine and the effect that reduces ox-LDL when regulating heart failure.In addition, the elegant jessamine extract that is rich in puerarin has restraining effect to the ethanol intake of the rat of being addicted to drink; Radix Puerariae extract can make acute non-lymph sexual cell leukemia (ANLL) patient medullary cell bcl-2, c-myc expression of gene protein obviously reduce, and illustrates that Radix Puerariae extract can induce ANLL cell and HL-60 cell generation apoptosis.
Clinical study proves that puerarin has stronger effect to infarct size and heart function.(Shandong Medical University's journal such as Xu Rongyan, 200038 (4) 360-363) observe after 37 routine myocardial infarction patient Pu Lelin treated for two weeks, infarct size drops to 24.67% by 37.31% before treating, blood plasma lipide superoxide (LPO) and vascular endothelial cell number (CEC) significantly reduce, and red corpuscle superoxide dismutase (SOD) significantly raises, and shrink simultaneously left chamber and diastolic function improves.Studies show that puerarin has and reduces normal district and infarcted region myocardial oxygen consumption, alleviates the intracellular Ca2+ load, the retardance beta-receptor, limits infarct size expansion, stabilizing blood pressure and improve effect such as heart function.Puerarin adds Potassium Magnesium Aspartata evident in efficacy to AMI thrombolysis RA, and clinical symptom and heart function significantly improve.Puerarin also has the effect of short vascular endothelial growth factor sample, repeatedly, prolonged application, can promote the opening and the growth of the original survey branch vessel of ischemic myocardium, promotes new survey to prop up formation.When the ischemic myocardium oxygen requirement doubles, obtain the supply of normal blood oxygen by surveying Zhi Xunhuan, avoid anginal generation.(Huabei Coal Medical Sciences College's journal such as Li Weihou, 20002 (6) 611-612) 64 routine coronary heart disease and angina pectoris patients are used puerarin in treating 10-14d after, the course of treatment and symptom are obviously improved, always efficient reaches 93.8%, wherein obvious effective rate is 59.4%, total efficient of control group is 84.4%, although two groups of total efficient there was no significant differences (P＞0.05), but its obvious effective rate significant difference P＜0.05), electrocardiogram(ECG improvement rate is respectively 75.0% and 65.6%, both compare indifference, but more obvious to NST before and after the medication and ∑ ST result improvement, significant difference (P＜0.01).Influence to blood pressure mainly is that systolic pressure is descended, and the average systolic fall is 7.72% (P＜0.05) before and after the treatment.This medicine does not all have obvious influence to blood sugar, hepatic and renal function and blood biochemistry, and blood fat is had tangible regulating effect, but reducing cholesterol, glycerine three pure and mild low-density lipoproteins increases high-density lipoprotein (HDL).
Puerarin also has the effect of treatment acute cerebral infarction.50 routine acute cerebral infarction patients are divided into two groups at random, and observation group's 30 examples adopt puerarin 400mg,, control group 20 examples adopt Radix Salviae Miltiorrhizae Injection 10ml.Once a day.Back clinical effect contrast one course of treatment (14d), observation group's total effective rate 73.3%, control group total effective rate 40%, there were significant differences (P＜0.001).Hemorheology changes before and after the treatment of observation group case that there were significant differences (P＜0.001) (Zhang Jiaxiang, Li Zhigang, People's Armed Police medical college journal, 2001,10 (1): 25-26).Acute cerebral infarction 120 examples are divided into treatment group (A group) 68 example and control group (B group) 52 examples at random.Adopt the double blind control method, A group puerarin injection 2ml, B group water for injection 1ml.Once/day, 7 days/course of treatment.Clinical efficacy shows: A group treatment back 68 examples (being almost recovered+marked improvement) are respectively 45 examples (69.2%) and 23 examples (44.2%), two groups of significant differences (P＜0.01).The immuning positive cell number of A group leukocyte surface CD11a, CD18, CD18/CD11a (LFA-1) obviously reduces (P＜0.05) before the treatment.The prompting puerarin increase the brain microcirculation volume of blood flow mechanism may with sealing leukocyte surface adhesion molecule CD11a, CD18 binding site, blocking leukocyte adheres to, suppresses the active relevant (Deng Juan etc. of PMNS with vascular endothelial cell, microcirculation magazine 2001,11 (1): 14-15).To vertebra-matrix artery blood supply insufficiency (VBI) effect better.102 routine VBI patients with vertigo are divided into two groups at random, and quiet of 60 routine puerarins are organized in treatment, quiet of control group 42 routine Ligustrazines.Treat observe the curative effect after 15 days, treatment group 13 examples of fully recovering, produce effects 19 examples, effective 23 examples, invalid 15 examples, total effective rate 91.7%; Control group 5 examples of fully recovering, produce effects 11 examples, effective 14 examples, invalid 2 examples, total effective rate 71.4%.Relatively there were significant differences (P＜0.01) for two groups of total effective rates.Each corresponding artery mean flow rate no significant difference (P＞0.05) before two groups of treatments, there were significant differences (P＜0.05) in the treatment back.There were significant differences (P＜0.05) before and after the treatment of control group, and the treatment group is then improved more remarkable (P＜0.01) (Zhu Linghua, time precious traditional Chinese medical science traditional Chinese medicines 200112 (2) 143-144).Wang faithful and upright person treats VBI patient's 40 examples, 17 examples of fully recovering, effective 20 examples, invalid 3 examples, total effective rate 94.1% (the Jiangsu traditional Chinese medical science 2001,22 (4): 12-13) with puerarin.Puerarin is to hypertension, pulmonary heart disease, and papillitis also has curative effect preferably.
The untoward reaction of puerarin is mainly heating, Cheng Weijin etc. (medicine prevailing disease magazine 20009 (3) 129-130) used the survey of patients of Pu Lelin to show to 568 examples, total incidence of heating is 5.81%, age, gender difference do not have significance, between just organizing, per daily dose do not have significant difference yet, and main relevant with the SM fate.The drug withdrawal or the processing of bringing down a fever simultaneously, body temperature is reduced to normally gradually.Antibiotic therapy is invalid.This may be because the course of treatment be long, and drug accumulation causes toxic action; Medicine sees through hemato encephalic barrier, directly stimulates the hypothalamus center of body temperature regulation, influences human body heat production and heat radiation process; And tardy parasexuality send out should.The anaphylaxis that puerarin also can cause.31 routine patients are with puerarin person 14 examples, 11 examples of wherein generating heat, fash 4 examples, 2 examples of suffering from abdominal pain, pain in the back 2 examples, haemolysis 2 examples; With Pu Lelin person's 17 examples, 12 examples of generating heat, fash 5 examples, 4 examples of suffering from abdominal pain, pain in the back 1 example, haemolysis 2 examples, anaphylactic shock 2 examples.Heating, fash, itch and stomachache all can spontaneous remission (the flat Liu Yu Xiang of Ye Yan etc., Chinese Journal of New Drugs, 2001,10 (4): 289-290) after in time finding also drug withdrawal.Puerarin injection once caused drug eruption 1 example.Pu Lelin causes the property a crossed hemoglobinuria 1 example, and mechanism it be unclear that.
Once the phenolic hydroxyl group and the sugar alcohol hydroxyl of puerarin were modified, synthesized a series of esters and ether derivative (Yang Ruolin, Li Na etc., China Medicine University's journal, 1999,30 (2): 81-85).But its drug effect and toxicity to cardiovascular and cerebrovascular is furtherd investigate.
Puerarin water-soluble and fat-soluble all very poor, its solubleness in water is 0.462g/100ml.Need to add solubility promoter in the preparation, commonly used have a polyvinylpyrrolidone (PVP) etc.Puerarin solubleness is 1.332g/100ml in the 4.3%PVP aqueous solution.PH is also influential to the solubleness of puerarin, the puerarin aqueous solution when pH is higher, its less stable.In puerarin complexing hydrotropy process, pH should be controlled at (Wu Zhenghong Zhu Yan duty etc., Jiangsu pharmacy and clinical study, 1999,7 (1): 9-12) below 6.5 usually.
The puerarin oral bioavailability is relatively poor, is about 30%, clinically is generally quiet notes administration.The puerarin poorly water-soluble, the drawbacks limit of oral administration biaavailability difference and existing side reaction its as medicinal value.
In existing document, do not see the report of the present invention's the puerarin compounds that contains water soluble group so far as yet, and they are in the purposes that relates to aspect the cardiovascular disease prevention effect.
Summary of the invention
In order to overcome the deficiencies in the prior art, the object of the present invention is to provide a class to contain the water soluble puerarin compound of Mannich alkali;
Another object of the present invention is to provide preparation to contain the method that the Mannich bases replaces the puerarin compound;
A further object of the present invention is to provide a kind of pharmaceutical composition that contains one or more this compounds;
Another purpose of the present invention is to provide a kind of purposes in the medicine of control cardiovascular and cerebrovascular diseases especially ischemic and anoxic relative disease.
In order to finish the present invention's purpose, the present invention takes following technical scheme:
The present invention relates to have the novel puerarin compound shown in the general formula I:
Figure C0215941800101
In the formula,
R 1And R 2The substituting group that is selected from respectively is a hydrogen, dimethylamino methyl, diethylin methyl, the di-n-propylamine ylmethyl, Diisopropylamine ylmethyl, Di-n-Butyl Amine ylmethyl, the diisobutylamine ylmethyl, two TERTIARY BUTYL AMINE ylmethyls, 1-Pyrrolidine ylmethyl, the piperidino methyl, the morpholinyl methyl, 1-six hydrogen piperazinyl methyl, N methyl piperazine ylmethyl, the TERTIARY BUTYL AMINE ylmethyl, the dicyclohexylamine methyl; R 1And R 2Different times table hydrogen; R 3Be selected from hydrogen, propionyl, butyryl radicals, isobutyryl, 2-methylbutyryl base, 3-methylbutyryl base, 2,2-dimethyl propylene acyl group, pentanoyl, caproyl, oenanthyl, capryloyl, nonanoyl, certain herbaceous plants with big flowers acyl group, lauroyl.Can be used as medicinal salt and contain to be selected from and can be used as medicinal various organic and inorganic carboxylate salt, comprise hydrochloric acid, Hydrogen bromide, phosphoric acid, phosphorous acid, sulfuric acid, methylsulfonic acid, tosic acid, toxilic acid, fumaric acid, tartrate, various natural or alpha-non-natural amino acids etc.
In order to prepare the compound described in the general formula I of the present invention, the present invention includes, puerarin raw material and suitable aldehyde and aminated compounds, in organic solvent, to reflux temperature, carry out the Mannich reaction, preparation corresponding M annich bases compound and salt thereof in room temperature.Specifically, suitable aldehyde comprises small molecules alkyl aldehydes and aromatic aldehyde and activated form thereof, as formaldehyde, and acetaldehyde, propionic aldehyde, different propionic aldehyde, two dimethylin methane, two diethylin methane, phenyl aldehyde, substituted benzaldehyde etc.; Solvent comprises water, lower alcohol, and lower alcohol is selected from methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, the trimethyl carbinol, isopropylcarbinol, amylalcohol, tert-pentanol, amylalcohol-2, amyl alcohol-3, hexanol etc.
Compound involved in the present invention, the solubleness in the water is better than puerarin at normal temperatures.
The invention still further relates to a kind of pharmaceutical composition that contains medicine effective dose as described compound of general formula I and pharmaceutically acceptable carrier.
Pharmaceutical research shows that compound of Formula I of the present invention has blood vessel is had the diastole effect; To cause the death time of mouse because of anoxic, The compounds of this invention has tangible prolongation effect; At the isolated rat heart ischemia reperfusion injury provide protection is arranged.The compounds of this invention has vasorelaxation action, and the coronary artery dilator and the cerebrovascular are arranged, and reduces myocardial consumption of oxygen, and microcirculation improvement and antiplatelet effects have potential control cardiovascular and cerebrovascular ischemic and anoxia functions.
The compounds of this invention is the new compound that a class has the puerarin parent nucleus, and they can be used for prevention and treatment coronary heart disease, various stenocardia, myocardial infarction, cerebro-vascular diseases.
Use pharmaceutical carrier well known to those skilled in the art can make the pharmaceutical composition of the The compounds of this invention that contains effective dose.
The compounds of this invention or its composition can be with oral methods or the medications of parenteral road.Oral medication can be tablet, capsule, Drug coating, non-ly through the intestines drug formulation injection and suppository etc. be arranged.These preparations are according to the known method preparation of those skilled in the art.In order to make tablet, capsule, the used auxiliary material of Drug coating is the auxiliary agent of conventional usefulness, starch for example, gelatin, gum arabic, silica, polyoxyethylene glycol, the used solvent of liquid dosage form is water for example, ethanol, propylene glycol, plant oil such as Semen Maydis oil, peanut oil, olive wet goods.Containing in the preparation of The compounds of this invention also can have other auxiliary agent, tensio-active agent for example, lubricant, disintegrating agent, sanitas, correctives, pigment etc.On the other hand, therefore the water-soluble puerarin that is better than of The compounds of this invention is easy to make the control that the whole body drug-delivery preparation is used for cardiovascular and cerebrovascular diseases.
The dosage that contains formula I compound of the present invention in tablet, capsule, Drug coating, injection and suppository is that the compound amount that exists in unit dosage form is calculated.The general content of formula I compound of the present invention is 10-500mg in unit dosage form, and preferred unit dosage form contains 20-200mg.
The invention will be further described below with reference to embodiment, but do not limit the scope of the invention.
Determining instrument used herein is fusing point XY-1 type electric heating fusing point instrument, NMR (Nuclear Magnetic Resonance) spectrum JNM-ECA-400 type nuclear magnetic resonance analyser.
Embodiment 1
Get the 560mg puerarin, mix, add 1ml33% dimethylamine agueous solution and 0.3ml 37% formalin with the 40ml dehydrated alcohol.Oil bath reflux 5 hours.Distillation removes and desolvates.Silica gel column chromatography gets the faint yellow crystallization of 340mg.mp195-196℃。 1H?NMR(CDCl 3)：8.33(1H，s，2-ArH)，7.94(1H，d，5-ArH)，7.35(1H，d，6-ArH)，7.34(1H，s，2’-ArH)，6.99(1H，d，5’-ArH)，6.78(1H，d，4’-ArH)，4.83(1H，d)，4.03(1H，t)，3.72(1H，d)，3.47(1H，m)，3.27(3H，m)，3.18(2H，s)，2.28(6H，s，N(CH 3) 2)。
Embodiment 2
Get the 280mg puerarin, be dissolved in the 20ml dehydrated alcohol, add 0.5ml diethylamine solution and 0.2ml 37% formalin.Oil bath reflux 7 hours.Distillation removes and desolvates.Silica gel column chromatography gets the faint yellow crystallization of 70mg.mp162-165℃。 1H?NMR(CDCl 3)：8.31(1H，s，2-ArH)，7.96(1H，d，5-ArH)，7.30(1H，d，6-ArH)，7.32(1H，s，2’-ArH)，6.98(1H，d，5’-ArH)，6.75(1H，d，4’-ArH)，4.85(1H，d)，4.05(1H，t)，3.70(1H，d)，3.45(1H，m)，3.30(3H，m)，3.15(2H，s)，2.26(4H，br，2NCH 2)，1.80(6H，t，2CH 3)。
Embodiment 3
Get the 280mg puerarin, be dissolved in the 20ml dehydrated alcohol, add 0.5ml Pyrrolidine solution and 0.2ml 37% formalin.Oil bath reflux 10 hours.Distillation removes and desolvates.Silica gel column chromatography gets the faint yellow crystallization of 50mg.mp155-156℃。1H?NMR(CDCl 3)：8.35(1H，s，2-ArH)，7.94(1H，d，5-ArH)，7.30(1H，d，6-ArH)，7.33(1H，s，2’-ArH)，6.97(1H，d，5’-ArH)，6.78(1H，d，4’-ArH)，4.85(1H，d)，4.00(1H，t)，3.71(1H，d)，3.48(1H，m)，3.26(3H，m)，3.16(2H，s)，2.28(4H，br，2NCH 2)，1.6-2.1(4H，br，2CH 2)。
Embodiment 4
Get the 280mg puerarin, be dissolved in the 20ml dehydrated alcohol, add 0.5m1N-methylpiperazine solution and 0.2ml 37% formalin.Oil bath reflux 14 hours.Distillation removes and desolvates.Silica gel column chromatography gets the faint yellow crystallization of 40m g.mp171-173℃。 1H?NMR(CDCl 3)：8.31(1H，s，2-ArH)，7.95(1H，d，5-ArH)，7.35(1H，d，6-ArH)，7.30(1H，s，2’-ArH)，7.00(1H，d，5’-ArH)，6.91(1H，d，4’-ArH)，4.87(1H，d)，4.05(1H，t)，3.72(1H，d)，3.48(1H，m)，3.20(3H，m)，3.16(2H，s)，2.00-2.28(8H，br，4NCH 2)，1.98(3H，s，CH 3)。
Experimental example 1: extracorporeal blood vessel ring dilation test
The method that this experiment adopts those skilled in the art to be familiar with is carried out.
After the wistar rat sacrificed by decapitation, open the chest abdomen rapidly, get aorta chest abdomen section, place the culture dish that fills vascular nutrition liquid, the separating blood vessel surrounding tissue, be cut into the artery bar that is about 3mm, the Stainless Steel Wire that two diameters are about 0.1mm carefully penetrates respectively, forms three square rings, with being placed in 37 ℃ of thermostatic baths that fill 10mg hemotrophic nutrition liquid, fixing and link to each other with tension pick-up, signal is further imported automatic desk-top balance recorder, feeding 95%O2 and 5% gas mixture.Begin the plansifter medicine after stable. after making that with norepinephrine vasoconstriction reaches the maximum collapse balance, get 0.1ml candidate drug solution and add in the bath, make drug level reach 10 -5M observed 10 minutes.Change and add norepinephrine behind the liquid and make vasoconstriction reach maximum value, use 10 then -6The Ach of M detects the integrity of blood vessel endothelium.Shrinkage amplitude after measuring maximum shrinkage amplitude and administration on the waveform recording figure calculates diastolic rate.
Experimental example 2: mouse normal pressure hypoxia endurance test
The method that this experiment adopts those skilled in the art to be familiar with is carried out.24 of Kunming mouses, male and female half and half.Be divided into control group and administration group at random, every group of each 12 animal.Behind the intraperitoneal injection test solution, place wide-necked bottle, sealing.The record death time.
Figure C0215941800151
Through above-mentioned test-results, those skilled in the art know, and compound of the present invention has the effect of anti-hypoxia ischemic to dried meat breast animal.The present invention comprises that preparation dried meat breast animal people's anti-cardiovascular medicament especially has good prospect in the application of anti-hypoxia and ischemic medicine.

Claims (8)

1. the puerarin compound that contains water-soluble group shown in general formula:
Figure C021594180002C1
In the formula, R 2For being selected from dimethylamino methyl, diethylin methyl, a kind of in 1-Pyrrolidine ylmethyl and the 4-methylpiperazine ylmethyl.
2. compound according to claim 1 is characterized in that R in the compound 2Be dimethylamino methyl.
3. compound according to claim 1 is characterized in that R in the compound 2Be the diethylin methyl.
4. compound according to claim 1 is characterized in that R in the compound 2Be 1-Pyrrolidine ylmethyl.
5. compound according to claim 1 is characterized in that R in the compound 2Be 4-methylpiperazine ylmethyl.
6. method for preparing the described compound of claim 1, it is characterized in that, with puerarin raw material and corresponding aldehyde or its etc. when thing and aminated compounds, in water and lower alcohol solvent and room temperature to reflux temperature, carry out the Mannich reaction, preparation corresponding M annich bases compound and salt thereof; Described lower alcohol is for being selected from methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, the trimethyl carbinol, isopropylcarbinol, amylalcohol, tert-pentanol, amylalcohol-2, a kind of in amyl alcohol-3 and the hexanol.
7. the application of the described compound of claim 1 in preparation medicament against cardiovascular disease and ischemia resisting or anoxic medicine.
8. one kind contains the described compound of claim 1 of medicine effective dose and the pharmaceutical composition of pharmaceutically acceptable carrier.
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