CN1183150C - Prepn process, medicine prepn and new medicinal use of sophoricosids - Google Patents

Abstract

The present invention discloses a new method for extracting and preparing high-purity sophoricoside from the fructus sophorae of traditional Chinese medicine in an industrialized mode and a medicinal preparation thereof, and also discloses new purposes of the sophoricoside for preventing and treating coronary disease, angina pectoris, myocardial ischemia, cerebral thrombosis, etc. The new technology for preparing the sophoricoside is characterized in that the sophoricoside is prepared from water and alcohol without using ether which is easy to inflame and explode or the separation means, such as, acetidin and butanol extraction, macroporous resin column chromatography, etc. The method has low cost, no environmental pollution and high safety factors, and is suitable for industrialized large-scale preparation.

Description

The preparation method of sophoricoside, pharmaceutical preparation and new medical use

Technical field

The present invention relates to a kind of preparation method, pharmaceutical preparation and new medical use of natural plant extracts, particularly relate to the invention of extraction novel preparation method, pharmaceutical preparation and the new purposes thereof of sophoricoside.

Background technology

The Fructus Sophorae, the different name Chinese scholartree is real, is the dry mature fruit of leguminous plants Chinese scholartree (Sophora japonica L.), the treatment of diseases such as the traditional Chinese medical science is mainly used in that bleeding hemorrhoids, intestines heat are had blood in stool, the headache of liver heat and hypertension.Contain abundant rutin, genistein, sophorabioside, sophoricoside, kaempferol etc. in the Fructus Sophorae.According to the literature, sophoricoside, genistein and kaempferol have certain estrogen effect and antifertility activity; The rutin that is contained has anti-inflammatory action, the effect of vitamin P sample, and has the effect of reducing blood-fat and protection lipid peroxidase and antioxidant enzyme.Sophoricoside (sophoricoside, structure be genistein-4 '-glucoside) be stored in the Chinese medicine Fructus Sophorae, not not extracting before the present invention and the sophoricoside monomer being made the pharmaceutical dosage form that allows on the pharmaceutics and be used for coronary heart disease and the report of aspects such as prevention and treatment of diseases such as cerebral thrombosis, more there is not launch related to the present invention about the sophoricoside industrialization.In in the past Fructus Sophorae total flavones or monomeric compound leaching process, generally all adopt sherwood oil or ether take off ester and with methods such as ethyl acetate, n-butanol extraction, macroporous resin or silicagel column separate, purifying.Used extraction solvent majority belongs to inflammable, explosive hazardous substance, and the production cycle is longer, cost is also higher, environment is also polluted, with sophoricoside be raw material development dripping pill, tablet, capsule, injection, aerosol be used for coronary heart disease, stenocardia, cerebral thrombosis, etc. disease before the present invention, do not appear in the newspapers yet.

Sophoricoside is a kind of isoflavonoid, and content is about 0.8-1.4% in the Fructus Sophorae, in medicinal material the sophoricoside major part be with plant in starch combine existence, also have plenty of the disaccharide glycosides, therefore the sophoricoside yield with general method extraction is lower.The structure of sophoricoside (Sophoricoside):

Genistein-4 '-glucoside (genistein-4 '-glucoside)

R＝β-D-Glu

Summary of the invention

One of purpose of the present invention has provided a kind of preparation method that sophoricoside is produced in industrialization that is suitable for; Two of purpose of the present invention provided with sophoricoside be main medicine or with pharmaceutical preparations such as the dripping pill of other medicines prescription, aerosol, tablet, capsule, injection.

Three of purpose of the present invention has provided with the application of sophoricoside in the medicine of diseases such as prevention and treatment coronary heart disease, stenocardia.

The preparation method of sophoricoside can be selected from a kind of in the following method:

1, with the Fructus Sophorae is raw material, be incubated enzymolysis 24 hours with per kilogram medicinal material 8-15g saccharifying enzyme or amylase 30-38 ℃ of water earlier, use 85-95% ethanol, ethanol liquid is transferred pH value 9-10 with sodium hydroxide, refluxing extraction 2-4 hour, filter, used the 70-80% alcohol reflux again 1-3 hour, extracted twice liquid is merged, transfer PH to 5-6, add medicinal activated carbon decolorizing with hydrochloric acid, decompression and solvent recovery, concentrated solution placement, filtration or centrifugal, the dry sophoricoside crude product that gets are used 95% ethyl alcohol recrystallization, get faint yellow crystallization.

2, with the Fructus Sophorae be raw material, soaked enzymolysis 12 hours with per kilogram medicinal material 8-15g saccharifying enzyme or amylase 30-38 ℃ of water insulation earlier, soaked medicinal material 12 hours with the per kilogram Fructus Sophorae with 20-40 gram calcium hydroxide milk of lime again, with 95% alcohol reflux 2-4 time, with activated carbon decolorizing, filtration, decompression recycling ethanol, placement, filtration or the centrifugal sophoricoside crude product that gets, use 95% ethyl alcohol recrystallization again, get subdiaphanous sophoricoside crystallization.

Particularly be that only water, ethanol and an amount of alkali just can industrialization prepare monomer sophoricoside crystalline method and belongs to initiative raw material in a large number with the Fructus Sophorae.Preparation method of the present invention has adopted 30-38 ℃ of insulation to soak, and utilizes the organized enzyme and exogenous organized enzyme (saccharifying enzyme or the amylase) natural enzymolysis that exist in the plant, and the organized enzyme natural enzymolysis adds an amount of alkaline degradation simultaneously when extracting.Facts have proved the method for utilizing this water logging insulation enzymolysis and alkaline degradation, improved the yield of sophoricoside widely, this method sophoricoside yield improves more than two times up to 3.0% than free state (can directly extract state) output in the former plant.Production technique of the present invention, with short production cycle, safe, free from environmental pollution, cost is low, the yield height, purity is particularly suitable for the industrialization mass production up to more than 95%.In view of the multiple biological activity of flavonoid compound (expanding hat, thrombolysis etc.), novel process of the present invention can be from the Fructus Sophorae industrialization prepare sophoricoside in a large number prospect in medicine widely will be arranged.

Aforesaid method of the present invention can be used for industrialization and prepare the monomer sophoricoside in a large number.Analyze by high performance liquid chromatography and liquid-matter coupling, the crystallisate of checking the inventive method preparation is exactly a sophoricoside.

1, high performance liquid phase (HPLC) is analyzed: instrument, U.S. Agillent1100 type high performance liquid chromatograph (joining quaternary pump, diode array detector, automatic sampler, column oven, software is the multiple several automated processing systems of Agillent1100 type).Condition: chromatographic column is Zorbax C ₁₈(4.6cm * 150cm), sample size is 5ul to the reverse phase silica gel post, and moving phase is methyl alcohol: water: glacial acetic acid=55: 40: 5, flow velocity are 1.0ml/min, and the detection wavelength is 359nm.Retention time is 2.181min, is symmetrical peak.

2, liquid-matter coupling (LC/MSD) is analyzed: instrument, U.S. Agillent liquid chromatograph/mass spectrometer (joining quaternary pump, compensating unit pump, diode array detector, automatic sampler, column oven, software is Agillent1100 type several data treatment system).Condition: chromatographic column is ZOBAX EXTEND C ₁₈Post, moving phase are acetonitrile: water (PH is 3.5)=80: 20.Flow velocity is 0.9ml/min, and the post post-compensation is urged ionization reagent ammonia soln (0.1ml/min), and the mass spectrum condition is negative ion mode (NEG) electron spray(ES) (API-ESI) scanning.Through liquid-matter coupling and high-efficient liquid phase analysis, and the compound that extracts in conjunction with the present invention of documents and materials proof is a sophoricoside.

Press practice of pharmacy, sophoricoside of the present invention can be prepared into the various clinical pharmaceutical dosage form, comprise the formulation of oral preparations or parenterai administration as treatment coronary heart disease and angina drug.Said oral preparations is selected from any in tablet, capsule, pill, granule, suspensoid, dripping pill, the oral liquid; Said non-enteron aisle is selected from a kind of in the middle of injection, aerosol or the subcutaneous administration formulation to formulation.

Medicine of the present invention preferably contains the sophoricoside of 1%-99% and the vehicle of 99%-1% (medicine that comprises other compatibility), preferably contain the sophoricoside of 30%-80% and the pharmaceutical excipient of 70%-20% (comprising the medicine that other compatibility is used), preferably contain the sophoricoside of 60%-70% and the vehicle of 40%-30% (comprising the medicine that other compatibility is used).

Auxiliary material in the medicine of the present invention is meant conventional vehicle, as solvent, disintegrating agent, correctives, sanitas, tinting material, tackiness agent etc.The medicine that other compatibility in the medicine of the present invention is used, the sophoricoside that refers to effective dose is certain medicine material, again compatibility other can allow the Chinese medicine or the pharmaceutical chemicals that share.

Sophoricoside pharmaceutical preparation of the present invention has effects such as treatment coronary heart disease, stenocardia, myocardial ischemia, cerebral thrombosis, is to be confirmed by following effect experiment.

Laboratory animal: healthy adult hybrid dog 12.5-17.5kg, the male and female dual-purpose is available from Norman Bethune Medical University laboratory animal portion; Kunming mouse, body weight 18-22g is available from the Jilin Prov. Inst. of Chinese Medicine and Chinese Medical Science animal feeding room; Rat, body weight 130-170g, the male and female dual-purpose is available from the institute for drug control, Jilin Province.

Test drug: sophoricoside is provided by Tianyao Science and Technology Co Ltd, Jilin.Lot number: 20020309.XINNAOSHUTONG JIAONANG, commercially available, produce lot number: 980205 by Taonan Jilin Pharmaceutical Co.

Experimental example 1Sophoricoside is to the influence of pure dog haemodynamics of fiber crops and myocardial consumption of oxygen

Test method:

Domesticated dog is fixed on the experiment table after with 3% vetanarcol (30mg/kg) intravenous anesthesia, cut downrights after, cut skin of neck, separate tracheae, intubate connects the phrenoton (WH-2 type, Tianjin Medical Appliance Factory produces).Separate femoral artery, intubate is measured arteriotony, separates external carotid artery and internal carotid artery, and the ligation external carotid artery overlaps suitable magnetic flow meter (MFV-1100 type, Japanese photoelectricity product) probe to measure cerebral blood flow (CBF) at internal carotid artery.Execute left side the 4th intercostal throacotomy, expose heart, cut off pericardium, make the pericardium bed, two-piece crown pulse artery LC and aortic root are placed the magnetic flow meter probe to measure coronary flow.Left ventricle apex intubate measurement left indoor pressure (LVSP), easypro end, left chamber are pressed (LVEDP) and maximum rising of left indoor pressure and fall off rate (± dp/dt max), are observed mark II lead electrocardiogram(ECG with limb leads, and calculate heart rate.Above index synchronous recording is in polygraph (RM-6000 type, Japanese photoelectricity product).The external jugular vein intubate is to coronary sinus vein, the carotid artery intubate, and (Kang Ni-158, the U.S. produces) measures the coronary sinus vein oxygen content of blood and arterial oxygen content respectively with blood oxygen determinator, with the calculating myocardium oxygen-consumption etc.After experiment finishes, dirty, the brain and weighing of coring, formula calculates the and the following index: heartbeat output, a series of two-level index such as total peripheral resistance, coronary resistance and cerebral vascular resistance.

The test grouping:

Test divides four groups, each 5 of every group of domesticated dogs, and first group is physiology saline control group, second group of positive medicine XINNAOSHUTONG JIAONANG (20mg/kg), third and fourth group are respectively and are subjected to little, the heavy dose of group (10mg/kg, 20mg/kg) of reagent.Stablize 10min after open chest surgery and intubate are finished, write down every index and be worth before as medicine.Along upper abdomen median line open abdomen, propose duodenum, give trial drug and physiological saline through duodenum, after administration, 15,30,45,60,90,120,150,180,210,240min carries out record, every record index and derivation parameter are carried out statistical procedures, relatively, judge its significance between organizing with the measured value of different observing times with the t check.

Test-results:

1, to anesthetized dog arteriotony, heart rate and Electrocardiographic influence

The physiological saline control group does not have considerable change to blood pressure, heart rate and electrocardiogram(ECG, and two dosage groups of positive drug control group and administration blood pressure self and physiological saline group after administration relatively have a declining tendency, but not statistically significant.Each group does not all have obvious influence (seeing Table, two) to heart rate, electrocardiogram(ECG

2, to the influence of anesthetized dog coronary flow and coronary artery resistance

Coronary flow and coronary artery resistance have no significant change before and after the administration of physiological saline control group, positive drug control group after administration 60-120 minute, coronary flow 103.26 ± 11.312 rises to 138.13 ± 16.41,145.31 ± 24.528 and 139.10 ± 19.623 (P＜0.01) before by medicine.The administration small dose group after administration 90 minutes by 99.97 ± 30.880 rising to 145.17 ± 33.263 (P＜0.05) before the medicine, the heavy dose of group of administration after administration 60-150 minute, by before the medicine 105.75 ± 19.470, be raised to 154.36 ± 30.548,167.34 ± 32.309,165.47 ± 23.561,148.85 ± 16.106 (P＜0.01), (seeing Table three).

Positive drug control group 90-120 minute coronary resistance 0.14 ± 0.029 before by medicine after administration reduced to 0.09 ± 0.011 and 0.09 ± 0.008 (P＜0.05).The administration small dose group was reduced to 0.08 ± 0.024 (P＜0.05) at 90 minutes by 0.14 ± 0.050 before the medicine.The heavy dose of group of administration reduced to 0.09 ± 0.011 at 60-120 minute by 0.14 ± 0.018 before the medicine, and 0.08 ± 0.009,0.08 ± 0.005 (P＜0.01) the results are shown in Table four.

3, easypro end, the left chamber of anesthetized dog left indoor pressure (LVSP) is pressed the influence of (LVEDP), the maximum climbing speed of left indoor pressure and maximum fall off rate (± dp/dt max) and the acting of left chamber.

Each group to anesthetized dog LVSP, LVEDP, ± acting of dp/dt max and left chamber do not have obviously influence, the results are shown in Table five, six, seven, eight, nine.

4, to the influence of anesthetized dog cardiac output, cardiac index and total peripheral resistance

Physiological saline control group, positive group medicine control group and administration small dose group do not have obvious effect to the anesthetized dog cardiac output, the heavy dose of group of administration after administration 90-120 minute, rise to 1.72 ± 0.399 by being worth 1.30 ± 0.257 before the medicine, 1.77 ± 0.475 (P＜0.05) see Table ten.

Each dosage group does not have obvious effect to cardiac index, sees Table 11.

Physiological saline control group, positive drug control group and administration small dose group do not have obvious effect to total peripheral resistance, and the heavy dose of group of administration after administration 90 minutes is reduced to 633.19 ± 112.51 (P＜0.05) by 953.64 ± 250.17 before the medicine, sees Table 12.

5, to the influence of anesthetized dog cerebral blood flow (CBF) and cerebral vascular resistance

The physiological saline control group does not all have obvious effect to anesthetized dog cerebral blood flow (CBF) and cerebral vascular resistance, positive drug control group was to cerebral blood flow (CBF) after administration 60-150 minute, rise to 573.24 ± 80.061 by 458.80 ± 82.637 before the medicine, 548.33 ± 96.905,575.29 ± 121.47,536.24 ± 101.00 (P＜0.05).Administration small dose group after administration 60-120 minute rises to 516.43 ± 74.840 by 437.74 ± 65.955 before the medicine, 534.45 ± 82.945,522.24 ± 90.637 (P＜0.05).569.85 ± 92.518,571.84 ± 80.287 (P＜0.01) saw Table 13 to the heavy dose of group of administration by 439.30 ± 71.234 rising to 545.41 ± 99.81 before the medicine in 60-120 minute after administration.

Positive drug control group after administration 60-180 minute, cerebral vascular resistance 0.03 ± 0.05 before by medicine reduces to 0.02 ± 0.003,0.02 ± 0.003,0.02 ± 0.04,0.02 ± 0.003,0.02 ± 0.004 (P＜0.05).Administration is little, heavy dose of group after administration 90 minutes, and by 0.003 ± 0.009,0.03 ± 0.008 reducing to 0.02 ± 0.006 before the medicine, 0.02 ± 0.005 (P＜0.05) sees Table 14 respectively.

6, to the influence of anesthetized dog heartbeat exponential sum heartbeat output

Each dosage group does not all have obvious effect to anesthetized dog heartbeat exponential sum heartbeat output, sees Table 15,16.

7, anesthesia is to the influence of dog myocardial consumption of oxygen oxygen consumption index and coefficient of oxygen utilization

The physiological saline control group does not all have obvious influence to myocardial consumption of oxygen, myocardial oxygen consumption index, myocardium coefficient of oxygen utilization.Positive drug control group 90-120 minute myocardial consumption of oxygen 9.40 ± 1.634 before by medicine after administration reduces to 4.44 ± 0.407,4.36 ± 1.482 (P＜0.01).The administration small dose group does not have considerable change to myocardial consumption of oxygen after administration.The heavy dose of group of administration after administration 45-120 minute reduces to 5.20 ± 0.952 by 8.93 ± 2.051 before the medicine, and 3.39 ± 1.256,5.21 ± 1.300,5.47 ± 1.947 (P＜0.01) see Table 17.

Positive drug control group, little, the heavy dose of group of administration does not all have obvious effect to the myocardial oxygen consumption index after administration, see Table 18.

Positive drug control group after administration 60-120 minute, coefficient of oxygen utilization 46.99 ± 6.369 before by medicine reduces to 24.89 ± 7.776,19.85 ± 4.609,20.01 ± 7.611 (P＜0.01).Little dose of group of administration do not have obvious effect to coefficient of oxygen utilization after administration.The heavy dose of group of administration after administration 45-120 minute reduces to 23.89 ± 5.314 by 43.89 ± 4.815 before the medicine, and 14.06 ± 4.859,19.08 ± 1.313,19.23 ± 4.625 (P＜0.001) see Table 19.

By above-mentioned experiment, confirmed that sophoricoside has the effect that improves blood supply of cardiac muscle and improve myocardial metabolism to anesthetized dog, cerebral blood flow increasing amount, myocardial blood flow, reduce cerebral vascular resistance, coronary resistance, myocardial consumption of oxygen and coefficient of oxygen utilization, thereby myocardial oxygen delivery is increased, improve the symptom of coronary heart disease and anginal hypoxic-ischemic, " pump " function of heart is strengthened, for clinical application provides rationale.

Experimental example 2Sophoricoside is to the function influence of anesthetized dog myocardial ischemia

Test method:

With domesticated dog with 3% vetanarcol (30mg/kg) intravenous anesthesia, separate tracheae, intubate connects breathing apparatus's (WH-2 type, Tianjin Medical Appliance Factory produces), the 4th intercostal is opened chest in the left side, expose heart, cut off pericardium, do the pericardium art and separate left anterior descending coronary artery, the stage casing threading is in order to ligation.Press infarct, marginarium, 24 epicardial leads of normal district's placement.Stablize 10min after operation is finished, measure normal epicardial electrogram then.Femoral venous catheter is got blood to measure AST, CK, LDH, does operation on duodenum and tests medicine and physiological saline, after administration 5,10,30,45,60,90,120,150,180,210,240,300,360min.The record epicardial electrogram, raising greater than 2mv with the S-T section is judging criterion, (S-T section total mv that raises is a ∑-ST), raises greater than the shared ratio of 2mv with the S-T section and calculates myocardial ischemia scope (N-ST) with this calculating myocardium degree of ischemia.Write down after 360 minutes, get blood for the second time, with AST, CK, LDH behind the mensuration medicine from femoral vein.Experiment is taken off heart after finishing, behind the normal saline flushing heart, the heavy whole-heartedly and left ventricular mass of weighing, be cut into 6 with left chamber is cross-section equably, place in nitro tetrazole orchid (N-BT) dye liquor, normal temperature dyeing 15min, measure the infarct (N-BT dye district) of every myocardium bilateral and non-infarct (N-BT dye district) outward with weighting method, every cardiac muscle is weighed, and calculates the weight of every cardiac muscle and the gross weight of infarct, calculates infarct and accounts for the left ventricle and the per-cent of dirty weight whole-heartedly.Get near fritter cardiac muscle (the coronary ligation line) and do pathological section, further observe the effect of medicine myocardial ischemia.

The test grouping:

Experiment divides four groups, each 5 of every group of domesticated dogs, and first group is physiology saline control group, second group of positive medicine XINNAOSHUTONG JIAONANG (20mg/kg) group, third and fourth group is for being subjected to little, heavy dose of organize (10mg/kg, the 20mg/kg) of reagent.

The experimental result statistics is judged its significance with measured value t check.

Test-results

(1) to the influence of anesthetized dog ischemic myocardium epicardial electrogram

1, to the degree of myocardial ischemia (influence of ∑-ST)

The physiological saline control group does not have obvious effect to ∑-ST after administration.Positive drug control group had obvious statistical significance (P＜0.01) in 60-240 minute after administration.Small dose group had obvious statistical significance (P＜0.05) in 60-120 minute after administration.Heavy dose of group after administration 45-240 minute has obvious statistical significance (P＜0.01).The results are shown in Table 20.

2, to the influence of myocardial ischemia scope (N-ST)

The physiological saline group does not have obvious effect to N-ST after administration, positive drug control group after administration 60-240 minute has tangible statistical significance (P＜0.05).Small dose group after administration 60-210 minute has statistical significance (P＜0.05).Heavy dose of group after administration 60-240 minute has tangible statistical significance (P＜0.01).See Table 21.

(2) to the influence of anesthetized dog Acute Myocardial Infarction area (N-BT staining mensuration)

The heavy dose of group of positive drug control group and administration compares with the salt solution group, can obviously dwindle myocardial infarct size (P＜0.01), and the effect of administration small dose group is not obvious, sees Table 22,23.

(3) to the influence of dog Acute Myocardial Infarction cardiac muscle three enzymes (AST, CK, LDH)

Each group does not all have obviously effect to myocardium three enzymes (AST, CK, LDH), sees Table 24,25,26.

Experimental example 3Influence to clotting time of mice

Get 50 of mouse, be divided into five groups at random, dosage sees Table 27, and every day 1 time, continuous irrigation stomach 15 days behind the last medicine 1 hour, adopts slide method to measure the clotting time.Experimental result proves: sophoricoside can make clotting time of mice prolong, and is remarkable with normal control group comparing difference.The results are shown in Table 27.

Experimental example 4To the hemorheological influence of blood stasis rat model

Get the wistar rat, male and female half and half are divided into six groups at random, press dosage gastric infusion shown in the table two 18, every day 1 time, continuous 15 days.Behind the last medicine 1 hour, except that the normal control group, all the other respectively organize rat skin lower injection suprarenin 0.08ml/100g, inject 1 time in 4 hours at interval, between biphasic injection suprarenin (front and back each 2 hours at interval) again, whole rats were immersed in the frozen water 5 minutes, dispose the back fasting, inferior rat aorta blood sampling in morning, anticoagulant heparin, give birth to LBY-N6A from clear rotational viscosimeter with Beijing Puli, measure rat whole blood viscosity and plasma viscosity.The result shows that sophoricoside can make the rat whole blood viscosity reduce, and is remarkable with the model group comparing difference.The results are shown in Table 28.

Table one sophoricoside is to the x ± SD that influences of anesthetized dog heart rate (inferior/minute)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 137.20 ± 14.772 137.80 ± 15.040 135.80 ± 15.222 129.00 ± 19.378 133.00 ± 12.748

Positive group 20mg/kg 153.80 ± 27.472 153.20 ± 29.098 145.80 ± 31.452 148.20 ± 29.346 133.00 ± 29.487

Medicine is given group 10mg/kg 154.40 ± 49.039 145.40 ± 49.848 148.20 ± 47.578 143.60 ± 48.752 145.00 ± 47.207

Medicine is given group 20mg/kg 139.40 ± 19.321 137.00 ± 16.538 136.20 ± 17.456 133.40 ± 18.165 133.80 ± 18.647

90 120 150 180 210 240min

133.40 ±28.192?133.40±24.214?131.80±24.325 133.60±19.295 129.60±21.571?128.00±21.213

134.00 ±23.119?124.20±26.109?126.00±13.820 125.20±12.276 120.60±16.288?121.60±14.605

147.80 ±44.60 142.40±40.575?142.00±39.064 139.80±38.545 139.80±34.974?140.40±33.321

130.20 ±18.660?127.80±20.389?124.20±17.167 123.60±16.273 127.40±21.220?124.40±22.165

Table two sophoricoside is to the x ± SD that influences of anaesthetized dog blood pressure (kPa)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 13.52 ± 1.527 13.39 ± 1.378 12.80 ± 1.229 13.26 ± 1.072 12.87 ± 0.403

Positive group 20mg/kg 14.17 ± 2.116 13.25 ± 1.960 13.14 ± 1.604 13.53 ± 1.091 12.47 ± 2.189

Administration group 10mg/kg 12.55 ± 2.904 12.36 ± 2.125 12.58 ± 2.258 12.41 ± 2.719 11.82 ± 2.375

Administration group 20mg/kg 14.76 ± 2.134 14.40 ± 1.715 14.03 ± 1.866 13.91 ± 1.402 13.79 ± 1.469

90 120 150 180 210 240min

12.18±0.903 11.47±1.732 12.25±1.601?12.49±1.659 12.21±1.498 12.29±1.627

12.57±1.070 12.03±1.194 11.78±1.421?11.17±1.964 11.13±1.823 11.50±1.883

11.42±1.781 11.15±1.565 10.98±1.897?11.11±1.965 11.13±2.065 11.12±1.883

13.29±1.592 13.48±1.543 13.06±1.656?13.28±1.778 13.09±1.477 12.80±1.223

Table three sophoricoside is to anesthetized dog myocardial blood flow (ml.100g ^-1Cardiac muscle .min ^-1) influence x ± SD

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 104.16 ± 21.703 108.95 ± 21.426 112.58 ± 24.84 114.53 ± 26.330 109.10 ± 19.524

Positive group 20mg/kg 103.26 ± 11.312 101.95 ± 13.480 111.50 ± 11.385 124.05 ± 11.528 138.13 ± 16.410*

Administration group 10mg/kg 99.97 ± 30.880 104.01 ± 33.638 105.32 ± 25.686 121.47 ± 31.175 136.18 ± 29.368

Administration group 20mg/kg 105.75 ± 19.570 107.58 ± 25.349 116.93 ± 27.166 130.43 ± 25.828 154.36 ± 30.548*

90 120 150 180 210 240min

103.84±15.301 97.12±15.693 98.19±26.089 97.82±18.679 99.92±18.802 94.80±28.844

145.31±24.528* 139.10±19.623** 127.97±22.975 100.75±12.318 94.69±11.767 94.76±13.568

145.17±33.263* 134.94±45.467 109.31±32.236 93.83±18.059 91.74±24.682 93.43±29.789

167.34±32.309** 165.47±23.561***?148.85±16.106** 101.43±11.697 100.50±15.820 94.84±24.244

Compare with the salt solution group: * P＜0.05, * * P＜0.01, * * * P＜0.001

Table four sophoricoside is to anesthetized dog coronary resistance (kPa.ml ^-1.100g ^-1Cardiac muscle .min ^-1) influence x ± SD

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 0.13 ± 0.027 0.13 ± 0.030 0.12 ± 0.033 0.12 ± 0.029 0.12 ± 0.018

Positive group 20mg/kg 0.14 ± 0.029 0.13 ± 0.018 0.12 ± 0.011 0.11 ± 0.013 0.09 ± 0.023

Administration group 10mg/kg 0.14 ± 0.050 0.13 ± 0.040 0.13 ± 0.038 0.11 ± 0.032 0.09 ± 0.024

Administration group 20mg/kg 0.14 ± 0.018 0.14 ± 0.021 0.12 ± 0.016 0.11 ± 0.012 0.09 ± 0.011*

90 120 150 180 210 240min

0.12±0.020 0.12±0.030 0.13±0.044 0.13±0.035 0.13±0.032 0.14±0.044

0.09±0.011* 0.09±0.008*?0.09±0.014 0.11±0.021 0.12±0.024 0.12±0.031

0.08±0.024* 0.09±0.038 0.11±0.037 0.12±0.032 0.13±0.036 0.13±0.042

0.08±0.0099**?0.08±0.005*?0.09±0.011 0.13±0.035 0.13±0.032 0.14±0.044

Compare with the salt solution group: * P＜0.05, * * P＜0.01

Table five sophoricoside is to the x ± SD that influences of anesthetized dog left indoor pressure (kPa)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 19.17 ± 2.677 19.17 ± 2.453 18.74 ± 2.491 19.12 ± 1.705 19.01 ± 1.691

Positive group 20mg/kg 20.02 ± 3.807 20.37 ± 4.718 21.57 ± 4.822 22.32 ± 5.439 20.21 ± 5.016

Administration group 10mg/kg 18.37 ± 3.305 18.24 ± 2.751 18.74 ± 1.910 18.21 ± 2.076 18.08 ± 3.940

Administration group 20mg/kg 20.61 ± 2.101 20.61 ± 1.625 20.29 ± 1.805 20.05 ± 1.997 20.10 ± 1.228

90 120 150 180 210 240min

17.76±2.625 18.00±3.243 18.18±2.962 18.77±3.052?17.95±2.855?18.18±2.845

20.18±4.044 18.69±2.745 17.94±2.775 17.49±2.890?18.02±3.795?18.32±3.338

18.05±2.922 17.84±3.144 17.97±3.166 17.28±2.160?16.82±1.577?16.37±0.963

19.98±1.660 19.51±1.604 19.62±1.906 19.46±0.842?19.44±0.915?19.14±1.270

Table six sophoricoside is pressed the x ± SD that influences of (kPa) to easypro end, chamber, an anesthetized dog left side

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 0.30 ± 0.058 0.43 ± 0.058 0.43 ± 0.109 0.43 ± 0.109 0.45 ± 0.121

Positive group 20mg/kg 0.45 ± 0.152 0.45 ± 0.071 0.48 ± 0.071 0.43 ± 0.173 0.37 ± 0.158

Administration group 10mg/kg 0.40 ± 0.130 0.45 ± 0.071 0.51 ± 0.112 0.48 ± 0.151 0.48 ± 0.071

Administration group 20mg/kg 0.40 ± 0.092 0.45 ± 0.071 0.50 ± 0.058 0.43 ± 0.058 0.38 ± 0.174

90 120 150 180 210 240

0.45±0.116 0.35±0.243 0.40±0.163 0.45±0.071 0.43±0.058 0.40±0.092

0.30±0.240 0.24±0.219 0.35±0.278 0.32±0.221 0.37±0.058 0.43±0.109

0.40±0.000 0.40±0.092 0.45±0.116 0.53±0.095 0.48±0.071 0.56±0.174

0.40±2.212 0.35±0.116 0.32±0.180 0.45±0.071 0.40±0.000 0.45±0.152

Table seven sophoricoside is to the x ± SD that influences of anesthetized dog ± dp/dt max (kPa/s)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 362.58 ± 97.227 397.23 ± 117.12 367.91 ± 165.58 413.23 ± 163.26 413.23 ± 133.96

Positive group 20mg/kg 293.26 ± 37.703 271.93 ± 63.650 325.25 ± 83.032 373.42 ± 37.703 233.59 ± 43.604

Administration group 10mg/kg 314.59 ± 85.145 317.25 ± 72.031 338.58 ± 66.383 303.92 ± 61.376 338.58 ± 88.220

Administration group 20mg/kg 381.24 ± 54.637 391.90 ± 59.315 463.88 ± 58.409 490.54 ± 131.42 463.88 ± 61.376

90 120 150 180 210 240

341.25±50.408?325.25±42.781?359.91±157.72?378.57±143.13?354.58±18.33 346.58±121.81

277.26±55.283?303.92±102.56?250.60±87.64 250.60±77.383?234.61±57.798?245.27±72.155

341.25±60.794?327.92±56.239?351.91±145.29?343.91±125.90?330.58±89.619?309.26±79.646

487.88±89.221?458.55±69.008?407.90±71.536?357.42±66.96 309.26±93.500?338.58±87.207

Table eight sophoricoside is to the x ± SD that influences of anesthetized dog-dp/dt max (kPa/s)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 237.27 ± 105.13 258.60 ± 67.708 242.61 ± 84.517 266.60 ± 96.124 279.93 ± 119.97

Positive group 20mg/kg 255.94 ± 76.807 223.94 ± 36.989 253.27 ± 36.506 253.27 ± 50.759 183.95 ± 40.432

Administration group 10mg/kg 186.62 ± 42.153 186.62 ± 62.523 197.28 ± 69.521 173.29 ± 44.211 250.60 ± 87.614

Administration group 20mg/kg 311.92 ± 39.543 327.92 ± 29.205 365.24 ± 101.34 335.92 ± 112.48 338.58 ± 57.798

90 120 150 180 210 240

215.95±42.573?191.95±40.651 199.95±67.970 183.95±71.412 202.62±66.916?183.95±71.402

162.63±30.397?162.63±23.845 151.96±34.760 149.30±23.845 141.30±20.216?146.63±13.330

205.28±39.543?194.62±43.807 210.61±40.432 186.62±57.334 197.28±55.283?186.62±47.79

314.59±66.383?301.26±79.758 277.26±51.970 242.61±27.318 258.60±20.216?255.94±40.432

Table nine sophoricoside is to anesthetized dog left side chamber acting (kg.m/min/m ²) influence x ± SD

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 0.36 ± 0.067 0.36 ± 0.057 0.35 ± 0.051 0.34 ± 0.059 0.33 ± 0.065

Positive group 20mg/kg 0.36 ± 0.077 0.36 ± 0.085 0.39 ± 0.141 0.40 ± 0.088 0.38 ± 0.112

Administration group 10mg/kg 0.32 ± 0.097 0.31 ± 0.083 0.33 ± 0.091 0.34 ± 0.099 0.32 ± 0.091

Administration group 20mg/kg 0.39 ± 0.097 0.40 ± 0.123 0.40 ± 0.129 0.44 ± 0.112 0.47 ± 0.141

90 120 150 180 210 240

0.31±0.073 0.29±0.090 0.30±0.082 0.31±0.080 0.29±0.090 0.28±0.089

0.36±0.082 0.32±0.083 0.29±0.073 0.27±0.088 0.26±0.074 0.26±0.064

0.30±0.073 0.28±0.074 0.27±0.078 0.27±0.075 0.25±0.061 0.25±0.064

0.48±0.179 0.50±0.192 0.38±0.124 0.36±0.095 0.34±0.087 0.33±0.078

Table ten sophoricoside is to the x ± SD that influences of anesthetized dog cardiac output (L/min)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 1.27 ± 0.216 1.30 ± 0.214 1.31 ± 0.188 1.24 ± 0.216 1.24 ± 0.246

Positive group 20mg/kg 1.22 ± 0.150 1.31 ± 0.110 1.39 ± 0.263 1.41 ± 0.166 1.45 ± 0.185

Administration group 10mg/kg 1.23 ± 0.192 1.24 ± 0.173 1.26 ± 0.163 1.31 ± 0.176 1.33 ± 0.197

Administration group 20mg/kg 1.30 ± 0.257 1.35 ± 0.334 1.39 ± 0.337 1.52 ± 0.290 1.65 ± 0.341

90 120 150 180 210 240

1.24±0.221 1.20±0.231 1.17±0.246 1.18±0.209 1.12±0.239 1.09±0.257

1.39±0.214 1.30±0.203 1.19±0.178 1.18±0.203 1.13±0.141 1.12±0.105

1.28±0.141 1.24±0.155 1.20±0.183 1.19±0.188 1.08±0.101 1.07±0.103

1.72±0.399* 1.77±0.475* 1.43±0.420 1.33±0.300 1.30±0.275 1.26±0.261

Compare with the salt solution group: * P＜0.05

Table ten sophoricoside is to the x ± SD that influences of anesthetized dog cardiac index (L/min/m2)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 1.95 ± 0.306 1.99 ± 0.296 2.00 ± 0.244 1.90 ± 0.308 1.89 ± 0.338

Positive group 20mg/kg 1.83 ± 0.175 1.97 ± 0.188 2.12 ± 0.524 2.14 ± 0.337 2.20 ± 0.364

Administration group 10mg/kg 1.83 ± 0.426 1.89 ± 0.408 1.92 ± 0.373 2.00 ± 0.401 2.02 ± 0.439

Administration group 20mg/kg 1.94 ± 0.291 2.00 ± 0.437 2.06 ± 0.447 2.28 ± 0.442 2.50 ± 0.607

90 120 150 180 210 240

1.90±0.331 1.85±0.345 1.80±0.378 1.82±0.323 1.72±0.368 1.68±0.397

2.12±0.417 1.97±0.390 1.81±0.353 1.79±0.363 1.71±0.238 1.69±0.178

1.95±0.386 1.89±0.397 1.84±0.419 1.82±0.393 1.64±0.246 1.63±0.285

2.61±0.729 2.67±0.825 2.14±0.606 2.00±0.445 1.94±0.376 1.90±0.392

Table ten two sophoricosides are to the x ± SD that influences of anesthetized dog total peripheral resistance (kPa/L/min)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 866.41 ± 145.57 840.44 ± 158.20 796.43 ± 145.22 879.84 ± 182.61 858.82 ± 174.65

Positive group 20mg/kg 941.70 ± 190.78 812.55 ± 116.86 764.56 ± 97.254 770.67 ± 75.776 688.07 ± 111.44

Administration group 10mg/kg 826.90 ± 208.76 808.80 ± 166.84 803.81 ± 139.37 762.18 ± 169.19 723.30 ± 171.79

Administration group 20mg/kg 935.64 ± 250.17 899.39 ± 267.07 841.47 ± 217.95 745.83 ± 113.97 681.59 ± 115.07

90 120 150 180 210 240

801.11±103.84 772.05±118.42?864.89±212.75?858.55±148.42?889.57±162.40?922.79±182.96

734.34±130.03 753.27±175.10?803.52±160.19?770.38±181.25?788.11±102.15?824.05±133.80

719.73±142.83 726.03±108.17?735.18±121.18?752.39±146.72?822.71±128.24?829.03±104.27

633.19±112.51*?637.13±146.23?773.74±237.61?829.14±234.08?831.54±192.85?836.89±194.64

Compare with the salt solution group: * P＜0.05

Table ten three sophoricosides are to the x ± SD that influences of anesthetized dog cerebral blood flow (CBF) (mL/100g.min)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 396.51 ± 61.010 404.04 ± 68.534 145.61 ± 77.077 412.23 ± 82.106 398.97 ± 68.567

Positive group 20mg/kg 458.80 ± 82.637 456.81 ± 79.580 475.20 ± 96.975 503.94 ± 88.300 573.24 ± 80.319**

Administration group 10mg/kg 437.74 ± 65.955 427.20 ± 81.278 456.79 ± 73.719 473.76 ± 75.477 516.43 ± 74.840*

Administration group 20mg/kg 439.30 ± 71.234 420.38 ± 65.523 459.87 ± 88.871 499.34 ± 78.325 545.41 ± 99.814*

90 120 150 180 210 240

384.99±63.061 375.24±56.591 380.45±66.425 374.6±64.048 373.51±68.716?359.31±56.693

548.33±96.905* 575.79±121.47* 536.24±101.00* 461.66±88.238?455.93±69.343?448.03±89.136

534.45±82.945* 522.24±90.637* 442.10±90.559 397.02±52.058?402.55±68.874?402.20±70.384

569.85±92.518**?571.84±80.278** 515.26±126.03 446.83±121.72?407.30±86.077?419.06±74.856

Compare with the salt solution group: * P＜0.05, * * P＜0.01

Table ten four sophoricosides are to the x ± SD that influences of anesthetized dog cerebral vascular resistance (kPa/ml/100g.min)

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 0.03 ± 0.007 0.03 ± 0.007 0.03 ± 0.008 0.03 ± 0.008 0.03 ± 0.007

Positive group 20mg/kg 0.03 ± 0.005 0.03 ± 0.005 0.03 ± 0.005 0.03 ± 0.003 0.02 ± 0.003**

Administration group 10mg/kg 0.03 ± 0.009 0.03 ± 0.007 0.03 ± 0.008 0.03 ± 0.008 0.02 ± 0.007

Administration group 20mg/kg 0.03 ± 0.008 0.03 ± 0.006 0.03 ± 0.006 0.03 ± 0.006 0.03 ± 0.005

90 120 150 180 210 240

0.03±0.007 0.03±0.009 0.03±0.007 0.03±0.008 0.03±0.009 0.04±0.009

0.02±0.003* 0.02±0.004*?0.02±0.003*?0.02±0.004*?0.02±0.004 0.03±0.005

0.02±0.006* 0.02±0.006 0.03±0.008 0.03±0.007 0.03±0.008 0.03±0.008

0.02±0.005* 0.02±0.005 0.03±0.008 0.03±0.010 0.03±0.008 0.03±0.006

Compare with the salt solution group: * P＜0.05, * * P＜0.01

Table ten five sophoricosides to anesthetized dog heartbeat index (L/min/m2/ time/min) influence x ± SD

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 14.39 ± 30.98 14.67 ± 3.073 14.94 ± 2.782 15.01 ± 3.342 14.36 ± 3.111

Positive group 20mg/kg 12.33 ± 3.086 13.19 ± 2.243 14.74 ± 2.854 14.75 ± 2.796 16.76 ± 1.910

Administration group 10mg/kg 12.93 ± 4.244 14.27 ± 6.048 13.87 ± 4.744 15.03 ± 5.403 14.91 ± 5.197

Administration group 20mg/kg 14.05 ± 2.358 14.73 ± 3.436 15.33 ± 3.686 17.41 ± 4.272 19.00 ± 5.358

90 120 150 180 210 240

14.76±3.813?14.76±3.590 13.99±3.563 13.80±2.921 13.60±3.538?13.46±3.963

15.79±1.221?15.97±2.047 14.34±1.829 14.26±1.969 14.22±1.324?13.97±1.198

13.98±4.225?13.97±4.375 13.56±4.229 13.75±4.607 12.20±3.032?11.98±2.950

20.42±6.478?22.13±8.561 17.43±4.817 16.41±3.938 15.69±2.968?15.75±4.254

Table ten six sophoricosides to anesthetized dog heartbeat output (L/min/ time/min) influence x ± SD

Value 15 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 9.42 ± 2.310 9.61 ± 2.284 9.80 ± 2.207 9.86 ± 2.688 9.43 ± 2.377

Positive group 20mg/kg 8.26 ± 2.461 8.82 ± 2.005 9.76 ± 1.810 9.80 ± 1.998 11.16 ± 1.696

Administration group 10mg/kg 8.46 ± 2.349 9.25 ± 3.126 9.04 ± 2.442 9.82 ± 3.017 9.78 ± 3.025

Administration group 20mg/kg 9.40 ± 1.701 9.87 ± 2.433 10.25 ± 2.537 11.53 ± 2.448 12.52 ± 2.778

90 120 150 180 210 240

9.71±2.924 9.35±2.618 9.17±2.632 9.02±2.141 8.94±2.562 8.83±2.813

10.50±1.397?10.57±1.127 9.49±1.132 9.47±1.406 9.47±1.419 9.31±1.398

9.19±2.421 9.14±2.367 8.89±2.361 9.01±2.658 8.04±1.746 7.86±1.438

13.40±3.269?14.48±4.468 11.62±3.175 10.89±2.343 10.43±1.762?10.41±2.483

Table ten seven sophoricosides are to anesthetized dog myocardial consumption of oxygen (ml.100g ^-1.min ^-1) influence (x ± SD n=5)

45 (min) 60 90 120 180 behind the value medicine before the group dosage medicine

Salt solution group (-) 8.26 ± 2.234 8.82 ± 2.344 8.17 ± 1.509 8.48 ± 1.437 7.84 ± 1.045 7.98 ± 1.978

Positive group 20mg/kg 9.40 ± 1.634 7.59 ± 2.330 5.92 ± 2.067 4.44 ± 0.407***, 4.36 ± 1.482** 6.97 ± 1.377

Administration group 10mg/kg 8.94 ± 3.374 8.37 ± 1.659 8.08 ± 3.299 8.11 ± 1.109 7.84 ± 2.593 7.82 ± 1.105

Administration group 20mg/kg 8.93 ± 2.051 5.20 ± 0.952*, 3.39 ± 1.256*** 5.21 ± 1.300** 5.47 ± 1.947* 7.47 ± 1.441

Compare with the salt solution group: * P＜0.05, * * P＜0.01, * * * P＜0.001

Table ten eight sophoricosides are (inferior/min.kPa) influence (x ± SD n=5) to anesthetized dog myocardial oxygen consumption index

Value 60 90 120 180 behind the value medicine before the group dosage medicine

45(min)

Salt solution group (-) 18.54 ± 2.771 17.16 ± 3.263 17.14 ± 2.008 16.15 ± 3.015 15.17 ± 2.725 16.72 ± 3.689

Positive group 20mg/kg 21.87 ± 5.448 20.05 ± 4.303 16.62 ± 4.915 16.95 ± 3.719 15.02 ± 3.925 14.09 ± 3.167

Administration group 10mg/kg 20.47 ± 12.085 18.73 ± 10.858 17.95 ± 9.531 17.30 ± 7.145 16.14 ± 5.929 16.02 ± 6.837

Administration group 20mg/kg 20.79 ± 5.123 18.70 ± 4.070 18.63 ± 4.163 17.43 ± 3.760 16.86 ± 3.784 16.32 ± 4.078

Table ten nine sophoricosides are to the influence (x ± SD n=5) of anesthetized dog cardiac muscle oxygen uptake rate (%)

Be worth 45 (min) 60 90 120 180 behind the value medicine before the group dosage medicine

Salt solution group (-) 40.95 ± 4.159 40.42 ± 5.544 39.49 ± 3.211 43.25 ± 5.361 42.35 ± 2.405 42.49 ± 3.430

Positive group 20mg/kg 46.99 ± 6.369 33.77 ± 7.962 24.89 ± 7.776**, 19.85 ± 4.609***, 20.01 ± 7.611*** 38.58 ± 5.434

Administration group 10mg/kg 46.54 ± 4.627 38.96 ± 6.480 33.11 ± 6.906 33.16 ± 8.159* 34.53 ± 10.624 45.46 ± 6.349

Administration group 20mg/kg 43.89 ± 4.815 23.89 ± 5.314**, 14.06 ± 4.859*** 19.08 ± 1.313*** 19.23 ± 4.625*** 39.54 ± 3.086

Compare with the salt solution group: * P＜0.05, * * P＜0.01, * * * P＜0.001

Value 5 10 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 5.80 ± 0.837 139.40 ± 29.190 146.80 ± 16.932 155.20 ± 18.019 147.80 ± 12.696 139.40 ± 21.279

Positive group 20mg/kg 5.80 ± 2.588 109.80 ± 19.652 128.20 ± 20.154 143.20 ± 20.474 128.80 ± 18.281 110.40 ± 12.759*

Administration group 10mg/kg 5.80 ± 1.095 124.00 ± 22.572 134.80 ± 18.780 146.20 ± 20.192 130.60 ± 17.544 111.60 ± 10.550*

Administration group 20mg/kg 4.60 ± 1.140 127.00 ± 16.703 138.00 ± 13.435 148.00 ± 5.292 132.20 ± 4.919*, 116.00 ± 4.637*

Table two ten sophoricosides are to (the influence (x ± SD n=5) of ∑-ST) of dog acute myocardial ischemia degree

90 120 150 180 210 240 300 360min

142.40±15.323 137.20±24.315 142.60±20.144 142.00±20.335 125.20±15.123 117.60±14.993?104.40±13.315?99.40±15.437

101.40±9.864** 95.40±8.204** 91.40±6.542***?92.00±4.637***?90.80±3.962** 96.00±6.000* 98.20±2.775 100.80±4.147

102.20±12.598**?91.80±13.535** 102.40±5.413**?109.80±14.704*?103.20±15.040* 102.40±14.363?101.80±16.084?102.40±18.889

104.000±8.485**?86.80±3.114** 88.00±4.899***?83.60±4.980***?93.00±4.583** 94.80±9.311**?101.80±9.497 105.20±7.950

Compare with the salt solution group: * P＜0.05, * * P＜0.01, * * * P＜0.001

Table two 11 sophoricosides are to the influence (x ± SD n=5) of dog acute myocardial ischemia scope (N-ST)

Value 5 10 30 45 60 behind the value medicine before the group dosage medicine

Salt solution group (-) 4.40 ± 1.817 18.00 ± 1.871 19.00 ± 1.000 18.00 ± 1.871 17.80 ± 2.864 18.00 ± 2.550

Positive group 20mg/kg 4.60 ± 1.673 15.40 ± 1.949 17.20 ± 16.43 17.20 ± 2.588 15.40 ± 1.817 13.20 ± 1.643**

Administration group 10mg/kg 3.40 ± 1.517 15.00 ± 2.236 18.40 ± 0.894 19.20 ± 1.304 16.60 ± 0.894 14.40 ± 1.140*

Administration group 20mg/kg 3.80 ± 1.304 17.00 ± 2.000 18.60 ± 0.894 17.80 ± 1.483 16.00 ± 1.225 13.60 ± 0.548**

90 120 150 180 210 240 300 360min

17.70±3.347 18.20±3.564 18.80±3.271 17.80±3.564 17.00±3.200 16.20±2.683 15.00±2.739 14.00±3.082

11.20±1.643** 12.60±0.548** 11.40±1.673** 10.80±1.643 11.40±2.191* 11.80±1.643* 12.00±1.581 11.40±1.140

12.20±1.095** 11.40±1.517** 12.40±1.817** 12.40±1.517* 12.60±1.140* 13.80±0.837 12.60±1.140 13.00±1.871

12.40±0.548** 12.00±1.225** 12.00±1.414** 11.00±0.707** 11.40±0.548**?11.20±0.87** 12.20±0.837 11.80±0.837

Compare with the salt solution group: * P＜0.05, * * P＜0.01, * * * P＜0.001

Table two 12 sophoricosides are to the influence (x ± SD n=5) of dog Acute Myocardial Infarction area (infraction/whole-heartedly)

360 (min) behind the group dosed administration

Salt solution group (-) 15.74 ± 1.041

Positive group 20mg/kg 12.88 ± 1.380**

Administration group 10mg/kg 14.46 ± 1.063

Administration group 20mg/kg 11.88 ± 1.112***

Compare with the salt solution group: * * P＜0.01, * * * P＜0.001

Table two 13 sophoricosides are to the influence (x ± SD n=5) of dog Acute Myocardial Infarction area (infraction/left ventricle)

360 (min) behind the group dosed administration

Salt solution group (-) 21.79 ± 2.159

Positive group 20mg/kg 17.16 ± 1.918**

Administration group 10mg/kg 20.12 ± 2.301

Administration group 20mg/kg 16.22 ± 1.764**

Compare with the salt solution group: * * P＜0.01

Table two 14 sophoricosides are to the influence (x ± SD n=5) of dog Acute Myocardial Infarction AST

360 (min) after the value administration before the group dosage medicine

Salt solution group (-) 36.00 ± 10.932 124.60 ± 57.908

Positive group 20mg/kg 46.80 ± 15.691 101.60 ± 42.454

Administration group 10mg/kg 31.00 ± 9.670 87.60 ± 9.555

Administration group 20mg/kg 29.60 ± 2.881 79.20 ± 10.780

Table two 15 sophoricosides are to the influence (x ± SD n=5) of dog Acute Myocardial Infarction CK

360 (min) after the value administration before the group dosage medicine

Salt solution group (-) 283.20 ± 118.68 1357.6 ± 478.15

Positive group 20mg/kg 388.20 ± 45.483 1125.8 ± 482.64

Administration group 10mg/kg 272.60 ± 82.358 1186.6 ± 179.72

Administration group 20mg/kg 299.80 ± 90.165 928.40 ± 358.92

Table two 16 sophoricosides are to the influence (x ± SD n=5) of dog Acute Myocardial Infarction LDH

360 (min) after the value administration before the group dosage medicine

Salt solution group (-) 114.60 ± 47.348 171.00 ± 63.565

Positive group 20mg/kg 113.80 ± 51.339 128.20 ± 37.352

Administration group 10mg/kg 97.60 ± 11.480 150.00 ± 28.320

Administration group 20mg/kg 91.00 ± 32.657 131.00 ± 34.648

The influence of 17 pairs of clotting time of mice of table two

The group dosage number of animals clotting time

n (min；X±SD

Control group 10 0.81 ± 0.14

Positive group 150mg/kg 10 1.02 ± 0.15 ^*

Administration group 150mg/kg 10 1.04 ± 0.15 ^*

75mg/kg 10 1.03±0.16 ^**

37.5mg/kg 10 0.96±0.17 ^*

Table two 18 sophoricosides are to the influence of blood stasis model hemorheology of rat (mpaS, X ± SD)

Group number of animals whole blood viscosity plasma viscosity

(mg/kg) (n) 10S ^-1 120S ^-1 40S ^-1 120S ^-1

Pseudo-operation group-10 9.17 ± 2.07 ^*4.28 ± 0.63 ^{* *}5.77 ± 0.81 ^{* *}1.07 ± 0.42 ^*

Model group-10 12.36 ± 2.76 5.99 ± 0.76 8.09 ± 1.15 1.61 ± 0.25

Positive group 100 10 10.25 ± 1.57 ^*5.15 ± 0.53 ^*6.70 ± 0.84 ^*1.51 ± 0.47

Administration group 100 10 9.57 ± 1.11 ^*4.7 ± 0.35 ^{* *}6.4 ± 0.61 ^{* *}1.16 ± 0.34 ^*

50 10 11.33±1.22 5.52±0.21 7.55±0.47 1.45±0.35

25 10 12.08±2.89 5.11±0.44 ^** 7.14±0.95 1.49±0.24

Above-mentioned experimental result shows that sophoricoside can obviously increase myocardial blood flow, reduces coronary resistance, reduce myocardial consumption of oxygen and oxygen uptake rate.These effects of sophoricoside, relevant with direct coronary artery dilating, make it myocardial blood flow and increase.Can reduce cardiac energy and oxygen consumption, oxygen uptake rate is reduced.The directly raising of reflection cardiac pumping function, the peripheral blood vessel expansion is relevant.Illustrate that sophoricoside can improve systema cariovasculare functional, regulate heart blood supply oxygen supply balance.

Experiment adopts ligation anterior descending coronary (LAD) to cause acute myocardial infarction model.With epimyocardium electrograph mapping degree of myocardial ischemia and scope, the variation of seroenzyme after quantitative tissue mensuration myocardial infarct size and the myocardial infarction.Experimental result proves that sophoricoside is through duodenal administration, and (∑-ST), reduce myocardial ischemia scope (N-ST) dwindles myocardial infarct size (MIS) obviously to reduce degree of myocardial ischemia.Illustrate that sophoricoside has function of resisting myocardial ischemia.

Simultaneously, sophoricoside can prolong clotting time of mice, and blood stasis rat model whole blood viscosity is reduced.Illustrate that sophoricoside has good function of promoting blood circulation to disperse blood clots.

In sum, sophoricoside is to preventing and treating cardiovascular disorder, and is significant as common diseases such as coronary heart disease, myocardial ischemias, also contains other activeconstituentss that are useful on prevention and treat coronary heart disease, stenocardia, cerebral thrombosis disease.

Embodiment

Embodiment 1

Fructus Sophorae 1kg adds 10g amylase, and 30-38 ℃ of water is incubated enzymolysis 24 hours, discard soak solution, with 95% ethanol 6000ml, ethanol liquid is transferred pH value 9-10 with sodium hydroxide, refluxing extraction 3 hours is filtered, and uses 80% alcohol reflux 2 hours again, extracted twice liquid is merged, transfer PH to 6, add medicinal gac 10g decolouring with hydrochloric acid, decompression and solvent recovery, concentrated solution placement, filtration or centrifugal, the dry sophoricoside crude product that gets are used 95% ethyl alcohol recrystallization again, get the about 30g of faint yellow crystallization, yield is 3%.

Embodiment 2

Fructus Sophorae 1kg adds the 10g saccharifying enzyme, and 30-38 ℃ of water insulation soaked 12 hours, discard soak solution, use milk of lime again, the per kilogram Fructus Sophorae restrains calcium hydroxides with 30, soaked medicinal material 12 hours, discard the milk of lime leach liquor,, merge extracted twice liquid with 95% ethanol 6000ml refluxing extraction twice, add gac 10g decolouring, filtration, decompression recycling ethanol, placement, filtration or the centrifugal sophoricoside crude product that gets, use 95% ethyl alcohol recrystallization again, get subdiaphanous sophoricoside crystallization 29g, yield is 2.9%.

Embodiment 3The preparation of capsule

Sophoricoside raw material 500g, medical starch 500g mixes, the 0# capsule of packing into, every 0.30g, each oral 1-2 grain, twice of every day.

Embodiment 4The preparation of tablet

Sophoricoside raw material 1000g, medical starch 500g mixes, and uses an amount of alcohol granulation, through the whole grain of pelletizing machine, compressing tablet, every 0.25g, oral, each 1-2 sheet, twice of every day.

Embodiment 5The preparation of granule

Sophoricoside raw material 100g, starch 1000g, Icing Sugar 400g mixes, and uses an amount of alcohol granulation, and dry, whole grain, packing are promptly.Oral, a 5g, twice on the one.

Embodiment 6The preparation of dripping pill

Take by weighing the 300g Macrogol 4000, in water-bath, melt, add sophoricoside raw material 100g, stir, in the impouring insulating pipe, regulate thermostat, make soup under 80-90 ℃, splash in the whiteruss that cooled off (temperature ± 4 ℃), after dripping off, to blot paraffin oil on the pill impouring filter paper, add a small amount of talcum powder again, mixing gets 1000 of sophoricoside dripping pills.Oral, a 2-3 grain, three times on the one, one after each meal.

Embodiment 7The preparation of injection

Sophoricoside raw material 10g, propylene glycol 20ml, polyoxyethylene glycol-400 50ml, water for injection 300ml mixes heating in water bath 30 minutes, add phenylcarbinol 50ml, add to 1000ml with water for injection again, in ultrasonic wave, handled 10 minutes, heated 30 minutes in the water-bath again, transfer pH value 5.5-6.5, filter clear and bright, embedding, the sterilization promptly.Every 2ml, intramuscular injection, a 2ml, 1-2 time on the one.

Claims (10)

1, sophoricoside extracts the method for preparation, it is characterized in that this method is selected from a kind of in the middle of following two kinds of methods:

A, be raw material with the Fructus Sophorae, 30-38 ℃ of water insulation enzymolysis 24 hours used 85-95% ethanol, ethanol liquid is transferred pH value 9-10 with sodium hydroxide, refluxing extraction 2-4 hour, filters, used the 70-80% alcohol reflux again 1-3 hour, extracted twice liquid is merged, transfer PH to 5-6, add medicinal activated carbon decolorizing with hydrochloric acid, decompression and solvent recovery, concentrated solution placement, filtration or centrifugal, the dry sophoricoside crude product that gets are used 95% ethyl alcohol recrystallization, get faint yellow crystallization;

B, be raw material with the Fructus Sophorae, 30-38 ℃ of water is incubated enzymolysis 12 hours, use milk of lime again, the per kilogram Fructus Sophorae restrains calcium hydroxide with 20-40, soaks medicinal material 12 hours, uses twice of 95% alcohol reflux again, with activated carbon decolorizing, filtration, decompression recycling ethanol, placement, filtration or centrifugal, get the sophoricoside crude product, use 95% ethyl alcohol recrystallization again, get subdiaphanous sophoricoside crystallization.

2, sophoricoside as claimed in claim 1 extracts the method for preparation, it is characterized in that this method is selected from a kind of in the middle of following two kinds of methods:

A. Fructus Sophorae per kilogram adds 10g amylase, and 30-38 ℃ of water is incubated enzymolysis 24 hours, discards soak solution, with 95% ethanol 6000ml, ethanol liquid is transferred pH value 9-10, refluxing extraction 3 hours with sodium hydroxide, filter, use 80% alcohol reflux 2 hours again, extracted twice liquid is merged, transfer PH to 6 with hydrochloric acid, add medicinal gac 10g decolouring, decompression and solvent recovery, concentrated solution placement, filtration or centrifugal, the dry sophoricoside crude product that gets, use 95% ethyl alcohol recrystallization again, get faint yellow crystallization.

B. Fructus Sophorae per kilogram adds the 10g saccharifying enzyme, 30-38 ℃ of water insulation soaked 12 hours, discarded soak solution, used milk of lime again, the per kilogram Fructus Sophorae restrains calcium hydroxides with 30, soaked medicinal material 12 hours, and discarded the milk of lime leach liquor, with twice of 95% ethanol 6000ml refluxing extraction, merge extracted twice liquid, add gac 10g decolouring, filtration, decompression recycling ethanol, placement, filtration or the centrifugal sophoricoside crude product that gets, use 95% ethyl alcohol recrystallization again, get subdiaphanous.

3, a kind of pharmaceutical preparation is characterized in that containing sophoricoside and one or more vehicle that pharmaceutically allow for the treatment of significant quantity.

4, pharmaceutical preparation according to claim 3 is characterized in that containing the sophoricoside of 1%-99% and the vehicle of 99%-1%.

5, pharmaceutical preparation according to claim 4 is characterized in that containing the sophoricoside of 30%-80% and the pharmaceutical excipient of 70%-20%.

6, pharmaceutical preparation according to claim 5 is characterized in that containing the sophoricoside of 60%-70% and the vehicle of 40%-30%.

7, pharmaceutical preparation according to claim 3 is characterized in that said medicine is the formulation of oral preparations or parenterai administration.

8, pharmaceutical preparation according to claim 7 is characterized in that said oral preparations is selected from a kind of in the middle of the tablet, pill, capsule, granule, suspensoid, dripping pill, oral liquid.

9, parenterai administration formulation according to claim 7 is selected from a kind of in the middle of injection, aerosol, suppository or the subcutaneous administration formulation.

10, sophoricoside is used for the application of the medicine of coronary heart disease, stenocardia, myocardial ischemia, cerebral thrombosis in preparation.