CN101926845A - Application of medicinal composition in preparation of medicament for treating coronary heart disease - Google Patents
Application of medicinal composition in preparation of medicament for treating coronary heart disease Download PDFInfo
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Abstract
The invention relates to new application of a medicinal composition in the field of pharmacy. The medicinal composition consists of euonymus fortunei, astragalus and red ginseng. Pharmacodynamics study proves that a medicament which is used for treating a coronary heart disease and prepared from the medicinal composition acts by enhancing cardiac contractility, reducing whole blood viscosity, plasma viscosity and whole blood reduction viscosity, decreasing oxygen consumption of myocardium and the like. No side or toxic effect is found during the clinical application of the medicament prepared from the medicinal composition.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of application of pharmaceutical composition in preparation treatment medicaments for coronary disease that contains Caulis Seu Folium Euonymi Fortunei, the Radix Astragali, Radix Ginseng Rubra.
Background technology:
In numerous diseases of harm humans, the cardiovascular diseases is one of the most common disease.It comes the disease prostatitis of serious threat modern society human health with tumor.And in the cardiovascular diseases, coronary heart disease is that morbidity is maximum, harm is the most intensive a kind of.Coronary heart disease is very general in developed country, though China compares with west industrially developed country, sickness rate is lower, and has also carried out positive control for many years, and incidence of coronary heart disease still is growing on and on.According to adding up in recent years, coronary heart disease accounts for about 10% of city death toll.In the intracardiac patient of section of China main big city hospital, coronary heart disease then accounts for more than 50%.Statistics over particularly past 10 years and discovering, the death rate of the onset at coronary heart disease age after 45 years old significantly increases, 70% morbidity and dead at 45-60 year age group is wherein arranged, has multiformity the crowd who suffers from coronary heart disease death, complexity, patient group's occupation comprises that politician, scientist, businessman, artist arrive ordinary people etc.., from above data as can be seen, coronary heart disease serious harm has arrived all trades and professions people's health and safety.
At present, Drug therapy, arteria coronaria interventional therapy and surgical intervention are three main thought of coronary heart disease modern treatment.And Chinese medicine has peculiar advantage as one of Drug therapy mode in China's clinical application.Chinese traditional treatment coronary heart disease has following characteristics, and the one, the traditional Chinese medical science is carried out corresponding specific aim treatment according to patient's various symptom determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs; The 2nd, carry out integrally-regulated to the patient; The 3rd,, treatment coronary heart disease " symptomatic treatment in acute condition, relieving the primary symptom in a chronic case ".Compare with Western medicine, Chinese medicine coronary heart disease has following 4 big advantages: toxic and side effects is less relatively, is suitable for prolonged application; A medicine can act on a plurality of pathology links of coronary heart disease; Improve symptom that the patient follows as breathe hard, weak, spirit depressing and sexual hypofunction etc. be comparatively obvious; Clinical and experimentation all proves, Chinese traditional treatment coronary heart disease has coronary artery dilator, improves myocardial ischemia, suppresses platelet aggregation, improves effects such as patient moving ability and quality of life, therefore the Chinese medicine medicine of exploitation treatment coronary heart disease promotes the people's health that positive role is arranged for the living standard that improves the people.
Summary of the invention
Through research for many years, the medicine of the preparation of pharmaceutical compositions of being made up of Caulis Seu Folium Euonymi Fortunei, the Radix Astragali, Radix Ginseng Rubra has therapeutical effect for coronary heart disease and a series of diseases of causing owing to ischemic heart desease.The object of the present invention is to provide the new purposes of aforementioned pharmaceutical compositions aspect preparation treatment medicaments for coronary disease.The therapeutic effect of the medicine of this preparation of pharmaceutical compositions is good, safe and reliable.
The weight proportion of each flavour of a drug that the prescription of this pharmaceutical composition is formed is as follows:
10～80 parts of Radix Ginseng Rubra, 10～400 parts of the Radixs Astragali, 10～1000 parts of Caulis Seu Folium Euonymi Fortuneis
This pharmaceutical composition is implemented by following proposal:
Implementation method 1: take by weighing Radix Ginseng Rubra and extract three times with 65% alcohol heating reflux, each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Take by weighing Caulis Seu Folium Euonymi Fortunei, the Radix Astragali, decoct with water secondary, decocted 2 hours at every turn, collecting decoction filters, and it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, add the ethanol of 2 times of amounts, the limit edged stirs evenly, leave standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, reclaim ethanol, concentrate, by preparation method adding filtrate (B), the adding appropriate amount of auxiliary materials of corresponding preparations, make preparation, promptly.
Implementation method 2. takes by weighing Radix Ginseng Rubra, the Radix Astragali, Caulis Seu Folium Euonymi Fortunei in proportion, and powder is beaten in oven dry respectively, and three's fine powder is mixed, and mixing adds adjuvant and makes suitable dosage form, promptly.
In order to understand the present invention better, at aspects such as myocardial ischemia test, myocardial oxygen consumption test and hemorheologys, study this medicine composite for curing coronary heart disease, the effect of ischemic heart desease below by the syrup formulation of this pharmaceutical composition
The specific embodiment
One, pharmacodynamic study
(1) product of the present invention is to the effect of Beagle dog myocardial infarction and ischemia model
1 material
1.1 medicine and reagent
Product of the present invention (syrup of this pharmaceutical composition), by method 1 preparation, being equivalent to the crude drug amount is 4.4946g/g, Coming-of-Age Day consumption be 30g.
FUFANG DANSHEN PIAN (abbreviation Radix Salviae Miltiorrhizae Tabellae), the heavy 0.317g of sheet, Beijing TongrenTang Pharmaceutical Co., Ltd's product, lot number are 8122615.
Pentobarbital sodium is Denmark's import packing, and lot number is 670213.
Heparin sodium injection is Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.'s product, and lot number is 081001.
Dextrose and Sodium Chloride Inj. is Hunan Cologne Pharmaceutical Co., Ltd's product, and lot number is C081214.
Sodium chloride injection is Hunan Cologne Pharmaceutical Co., Ltd's product, and lot number is D081204.
Chlorination nitro tetrazole orchid (NBT) is Suzhou Industrial Yacoo Chemical Reagent Co., Ltd.'s product, and lot number is YK2009020701.
The CK-MB test kit is the middle north control Science and Technology Co., Ltd. product of giving birth to, and lot number is 090301200905.
The LDH test kit is the middle north control Science and Technology Co., Ltd. product of giving birth to, and lot number is 090241200905.
Free fatty (FFA) and lactic acid (LA) test kit are Nanjing and build up bio-engineering research institute product, and lot number is 20090630.
1.2 animal
The Beagle dog is provided by Gaoyao City Condar laboratory animal Science and Technology Ltd., and the laboratory animal production licence number is SCXK (Guangdong) 2004-0009, and the laboratory animal quality certification number is 0049216.
1.3 instrument
The KONE-PRO automatic clinical chemistry analyzer is a Finland Kang Yi instrument company product.
ALC-V8 type animal respirator is a Shanghai Alcott bio tech ltd product.
ALC-ECG multiple tracks electrocardiogram instrument is a Shanghai Alcott bio tech ltd product.
MFV-1200 type electromagnetic blood flow meter is counted Japanese photoelectricity company product.
PowerLab 8/e type multi-path physiology analyser is an Australian ADI instrument company product.
S-22PC type visible spectrophotometer is Prism Optical Technology Co's product.
CY-3 type oxygen analyser is a Shanghai China light instrument and meter factory product.
GL-21 type High speed refrigerated centrifuge is centrifuge factory of a Hunan Instrument General Factory product.
2 methods
2.1 test method
Get 30 of Beagle dogs, body weight 9.25 ± 1.43 (8～11) kg, male and female half and half are divided into 5 groups by sex, body weight stratified random, each 3 of every group of male and female, sub-cage rearing, 1 in every cage is fed full-valence pellet feed, drinks cold boiled water; 22～25 ℃ of laboratory temperatures, humidity 50～70%.5 treated animals are given pure water, the basic, normal, high dosage group of product of the present invention (0.8,1.6,3.2g/kg) and Radix Salviae Miltiorrhizae Tabellae (0.076g/kg) respectively, and the administration volume is 1ml/kg, admix in the feedstuff oral, every day 1 time, administration 5 days.
Draw the Beagle dog behind the medicine, after weighing, from forelimb cephalic vein injection pentobarbital sodium 30mg/kg anesthesia, dorsal position is fixed on the operating-table, right side groin, chest, throat portion unhairing, sterilization;
Cut the about 1cm of skin in the right inguinal artery place of beating, passivity is separated the flesh layer, exposes femoral artery and femoral vein, and femoral venous catheter is in order to transfusion; Insert femoral artery with the YP100 type pressure transducer conduit that is full of heparin-saline and measure blood pressure.
Medisection skin of neck 3-5cm, passivity is separated the flesh layer, expose trachea, right carotid and external jugular vein, an osculum is cut in trachea the place ahead in the Thyreoidine below, insert threeway, connecting artificial respirator, is that 280-350ml practices artificial respiration with 15-20 time/min, respiratory quotient 2: 1, tidal volume, regulates respiratory frequency subsequently and autonomous respiration is synchronous.
The list of references method
[1], begin to xiphoid-process from presternum, cut skin along midsternal line with 932 type endotherm knifes, passivity is separated flesh layer, hemostasis by ligation; Cut off breastbone with the bone forceps center, passivity is cut pleura, and cutting shoulder is continued to use saline gauze and covered, and machine for chest-opening struts otch, exposes heart; Mention pericardium, cut off along the axle direction, the pericardium sutured on thoracic wall, is become a cradle shape in pericardium the place ahead; From vena femoralis injection 5mg/kg (625u/kg) heparin sodium and 4mg/kg lignocaine; Carefully mention the right auricle with Smooth forceps, cut an osculum, insert the coronary sinus sleeve pipe that is full of heparin-saline in the auricle tip, auricle otch and the effective cotton thread ligation of cover, the sleeve pipe other end inserts external jugular vein by conduit, and conduit connects FF030T type electromagnetic flowmeter probe, and keeps clearness of catheter; Then the coronary sinus conduit is carefully inserted in the coronary sinus vein of base of heart; Fall branch 1/2 place to penetrate No. 0 silk thread standby to the arteria coronaria below in coronary artery is left front; The outer membrane electrode of 16 breasts is covered a left front blood supply zone that falls, and with silk thread with Corner Strapped on visceral pericardium; The conduit two ends that will have threeway are inserted Carotid proximal part and distal end respectively, and keep clearness of catheter; Blood pressure transducer is connected with bridge amplifier, the electromagnetic flowmeter probe is connected with MFV-1200 type electromagnetic flowmeter, bridge amplifier and electromagnetic flowmeter insert PowerLab 8/e multi-path physiology analyser, with Chart 4.2.3 continuous record and the signal of analyzing collection; The outer membrane electrode of 16 breasts line that leads is connected with ALC-ECG type multiple tracks electrocardiogram instrument, adopts ALC software continuous record and analysis epicardial electrogram; Insert No. 14 stomach tubes in order to administration from the oral cavity; Treat the stable back administration of blood pressure, CBSF and epicardial electrogram, about 5min after the administration, the left front branch that falls of ligation arteria coronaria; Before the ligation coronary artery and after the ligation 1,2, gather common carotid artery blood and each 0.5ml oxygen determination dividing potential drop of coronary sinus blood during 3h respectively; Get coronary sinus blood 2.0ml, the centrifugal 10min of 3000rpm, separated plasma, in 2 0.5ml test tubes with cover of packing, put in-20 ℃ of refrigerators preserve standby; After the off-test, cut off ascending aorta, take out heart rapidly, put in the cold saline, peel off fat and non-myocardial vascular tissue, rinse well, the filter paper suck dry moisture is weighed, and separates left compartment muscle from coronary sulcus, and the postposition of weighing-20 a ℃ refrigerator and cooled is frozen 30-60min.
2.2 detection index
2.2.1 myocardial ischemia district ratio
Take out freezing left ventricle, myocardium sheet with sharp cutter crosscut Cheng Houyue 10mm, put into the 0.1%NBT solution of 37 ℃ of insulations, constantly stir, treat that the normal myocardium sheet blue back and take out, blot solution on the myocardium sheet with filter paper, weigh after wiping out painted cardiac muscle, with each myocardium sheet ischemic region weight, respectively divided by whole-heartedly, left ventricular mass, obtain that the ischemic region cardiac muscle accounts for whole-heartedly or the percentage ratio of left ventricle (%).
2.2.2 epicardial electrogram
Before the administration and after the administration 15,30,60,90,120,180min, analyze epicardial electrogram RR, QT interval and ST section, R and T ripple and change; Represent the degree of myocardial ischemia with ∑ Δ ST, with the scope of NST (refer to ST section move＞all animals ST section moves counting of meansigma methods) expression myocardial ischemia.
2.2.3 myocardial oxygen consumption
Before administration and after the administration 1,2,3h, survey arterial blood and coronary sinus blood oxygen pressure, definite blood oxygen saturation of tabling look-up with CY-3 type blood oxygen analyzer
[2], colorimetry is surveyed HgB concentration
[3], calculating myocardium oxygen consumption by formula.
HgB(g/L)＝OD
HgB×64458/44000×251＝OD
HgB×367.7
Oxygen consumption (ml/min/100g)=HgB/1000 * CF * 1.35 * (S
AO-S
VO)/HW
OD
HgBBe the optical density of the hemoglobin measured, S
AO, S
VOBe respectively arterial blood and Svo2 (%), CF is coronary flow (ml/min), and HW is cardiac weight (g).
2.2.4 blood plasma LDH, CK-MB activity and free fatty, lactic acid content
Before administration and after the administration 1,2,3h, survey blood plasma LDH and CK-MB activity with KONE PRO automatic biochemistry analyzer; Colorimetry S22PC spectrophotometric instrumentation blood plasma free fatty acid and lactic acid content.
2.2.5 coronary flow and coronary resistance
Before the administration and after the administration 15,30,60,120,180min, represent coronary flow (CBF) with the coronary sinus flow, with the ratio of diastolic pressure and coronary flow as coronary resistance.
2.2.6 blood pressure
Before administration and after the administration 15,30,60,120,180min, measure systolic arterial pressure, diastolic pressure and mean arterial pressure.
2.3 statistical analysis technique
With Microsoft Excel computation of mean values, standard deviation, relatively t check between organizing.
3 results
3.1 product of the present invention to Beagle dog coronary ligation after the influence of myocardial ischemia area
Fell before the dog heart coronary artery after the ligation 3 hours, myocardium sheet dyes through NBT, the normal myocardium tissue staining, and ishemic part cardiac muscular tissue does not dye.Pure water contrast dog, myocardial ischemia tissue weight accounts for 11.8% of myocardium weight whole-heartedly, accounts for 17.5% of myocardium of left ventricle weight; Compare with pure water, product 1.6 of the present invention, 3.2g/kg and FUFANG DANSHEN PIAN 0.076g/kg can obviously reduce ischemic myocardium and account for the ratio of cardiac muscle and myocardium of left ventricle weight whole-heartedly, and product 0.8g/kg of the present invention reduces the ischemia weight ratio but not statistically significant (table 1) slightly.
Table 1. product of the present invention to the influence of Beagle dog myocardial ischemia tissue weight (
N=6)
Compare with pure water:
*P＜0.05,
*P＜0.01.
3.2 product of the present invention to Beagle dog coronary ligation after the influence that changes of epicardial electrogram ST section
After falling a ligation before the dog coronary artery, all animals epicardial electrogram ST section is offset.15min to 180min after 30 animal ligation, 16 measurement points and 6 time point ST field offsets (Δ ST) population mean are 11.9mV.With the count (NST of Δ ST greater than population mean
1) and Δ ST greater than the (NST that counts of 1/2 population mean
2) as the scope of weighing myocardial ischemia, compare with pure water, product 0.8,1.6 of the present invention, 3.2g/kg and FUFANG DANSHEN PIAN 0.076g/kg all reduce NST
1And NST
2120min to 180min behind the coronary ligation, the basic, normal, high dosage of product of the present invention reduces NST
1Effect have remarkable meaning, the middle and high dosage of product of the present invention reduces NST
2Effect have remarkable meaning; FUFANG DANSHEN PIAN reduces NST
1And NST
2The effect highly significant, begin to continue to 180min (table 2) after the ligation behind the self-ligating.
With fall before the dog coronary artery before the ligation relatively, dog epicardial electrogram ST section obviously is offset after the ligation.Pure water contrast dog ST field offset (∑ Δ ST) is more serious, continues to 180min after the ligation.Compare with pure water, product 0.8,1.6 of the present invention, 3.2g/kg and FUFANG DANSHEN PIAN 0.076g/kg can alleviate ∑ Δ ST; The effect that 120min to 180min behind the coronary ligation, product of the present invention alleviate ∑ Δ ST has remarkable meaning, and the interior ∑ Δ ST of 60min changed slight after wherein high dose group had 1 routine ligation; FUFANG DANSHEN PIAN alleviates the effect highly significant of ∑ Δ ST, begins to continue to 180min (table 3) after the ligation behind the self-ligating.
Table 2. product of the present invention to Beagle dog coronary ligation after epicardial electrogram NST influence (
N=6)
Compare with pure water:
*P＜0.05,
*P＜0.01.
Table 3. product of the present invention to Beagle dog coronary ligation after epicardial electrogram ST section influence (
N=6)
Compare with pure water:
*P＜0.05,
*P＜0.01.
3.3 product of the present invention to Beagle dog coronary ligation after the influence of myocardial oxygen consumption
Before falling a ligation before the dog coronary artery, pure water matched group and administration treated animal myocardial oxygen consumption no significant difference.Compare with pure water, 60min to 180min after the ligation, product 1.6 of the present invention, 3.2g/kg and FUFANG DANSHEN PIAN 0.076g/kg significantly reduce myocardial oxygen consumption, and product 0.8g/kg of the present invention also has the effect that reduces myocardial oxygen consumption but not statistically significant (table 4).
Table 4. product of the present invention to Beagle dog coronary ligation after myocardial oxygen consumption (ml/min/100g) influence (
N=6)
Compare with pure water:
*P＜0.05.
3.4 product of the present invention to Beagle dog coronary ligation after blood plasma CK-MB and the active influence of LDH
Before falling a ligation before the dog coronary artery, the active no significant difference of pure water matched group and administration treated animal Plasma CK-MB and LDH.Compare with pure water, 120min to 180min after the ligation, product 1.6 of the present invention, 3.2g/kg significantly reduce CK-MB and LDH activity, and product 0.8g/kg reduction CK-MB of the present invention and the active effect of LDH are not remarkable; 60min to 180min after the ligation, FUFANG DANSHEN PIAN 0.076g/kg significantly reduce CK-MB activity (table 5).
Table 5. product of the present invention to Beagle dog coronary ligation after blood plasma CK-MB and the active influence of LDH (
N=6)
Compare with pure water:
*P＜0.05,
*P＜0.01.
3.5 product of the present invention to Beagle dog coronary ligation after the influence of blood plasma FFA and LA content
Before falling a ligation before the dog coronary artery, pure water matched group and administration treated animal plasma F FA and LA content no significant difference.
Compare with pure water, 120min to 180min after the ligation, product 1.6 of the present invention, 3.2g/kg and FUFANG DANSHEN PIAN 0.076g/kg significantly reduce FFA and LA content, and the effect of product 0.8g/kg reduction FFA of the present invention and LA content is remarkable (table 5) not.
Table 6. product of the present invention to Beagle dog coronary ligation after blood plasma FFA and LA content influence (
N=6)
Compare with pure water:
*P＜0.05,
*P＜0.01.
3.6 product of the present invention to Beagle dog coronary ligation after the influence of coronary flow
Compare with pure water, a ligation is fallen before the dog coronary artery and after, product 0.8,1.6 of the present invention, the not obvious change of 3.2g/kg animal CBF; FUFANG DANSHEN PIAN 0.076g/kg has the effect (table 7) that increases CBF.
Table 7. product of the present invention to Beagle dog coronary ligation after coronary flow influence (
N=6)
Compare with pure water:
*P＜0.05.
3.7 product of the present invention to Beagle dog coronary ligation after the influence of blood pressure
After falling a ligation before the dog coronary artery, animal SBP, DBP, MAP prolong in time and progressively descend.Compare product 0.8,1.6 of the present invention, 3.2g/kg and the not obvious change of FUFANG DANSHEN PIAN 0.076g/kg animal SBP, DBP, MAP (table 8) with pure water.
Table 8. product of the present invention to Beagle dog coronary ligation after blood pressure influence (
N=6)
3.8 product of the present invention to Beagle dog coronary ligation after Electrocardiographic influence
After falling a ligation before the dog coronary artery, the changing value of the animal epicardial electrogram R ripple and the T wave-wave width of cloth prolongs in time and progressively reduces, and RR interval, QT interval and HR do not have significant change.Compare with pure water, the changing value of the not obvious change of product 0.8,1.6 of the present invention, 3.2g/kg and the FUFANG DANSHEN PIAN 0.076g/kg animal epicardial electrogram R ripple and the T wave-wave width of cloth does not have obvious influence (table 9, table 10) to RR interval, QT interval and HR.
Table 9. product of the present invention to Beagle dog coronary ligation after epicardial electrogram R ripple and the T wave-wave width of cloth influence (
N=6)
Table 10. product of the present invention to Beagle dog coronary ligation after epicardial electrogram RR interval, QT interval and HR influence (
N=6)
4 conclusions
Product of the present invention is given Beagle dog oral administration 5 days, making a ligation is fallen before the heart coronary artery and after the ischemic myocardial tissue weight ratio obviously reduce, epicardial electrogram NST and ∑ Δ ST obviously descend, make that the myocardial ischemia scope is dwindled, degree of ischemia alleviates, myocardial oxygen consumption is reduced, show that product of the present invention has the effect that resists myocardial ischemia.
Because product of the present invention has protective effect to ischemic myocardium, and myocardial damage is alleviated, the LDH and the specific C K-MB that are discharged in the blood reduce, and CK-MB, LDH are active in the blood plasma obviously reduces; Simultaneously, cardiac muscle increases FFA and LA utilization rate, and plasma F FA, LA content are obviously descended.
Experimental result shows that product of the present invention does not have obvious influence to the heart coronary flow, does not also influence animal blood pressure, heart rate and epicardial electrogram RR, QT interval, to the nonsignificance that influences of the R ripple and the T wave-wave width of cloth.
(2) product of the present invention is to the hemodynamic influence of Beagle dog
1. test method
Get 25 of Beagle dogs, body weight 10.03 ± 1.06 (8～12) kg, male and female are regardless of, and are divided into 5 groups by sex, body weight stratified random, and every group female 3, male 2, sub-cage rearing, 1 in every cage is fed full-valence pellet feed, drinks cold boiled water.5 treated animals are given pure water, the basic, normal, high dosage group of product of the present invention (0.8,1.6,3.2g/kg) and Radix Salviae Miltiorrhizae Tabellae (0.076g/kg) respectively, and the administration volume is 1ml/kg, admix in the feedstuff oral, every day 1 time, administration 5 days.
Draw the Beagle dog behind the medicine, after weighing, from forelimb cephalic vein injection pentobarbital sodium 30mg/kg anesthesia, dorsal position is fixed on the operating-table, right side groin, chest, throat portion unhairing, sterilization; Cut the about 1cm of skin in the right inguinal artery place of beating, passivity is separated the flesh layer, exposes femoral artery and femoral vein, and femoral venous catheter is in order to transfusion; Insert femoral artery with the YP100 type pressure transducer conduit that is full of heparin-saline and measure blood pressure; Medisection skin of neck 3-5cm, passivity is separated the flesh layer, expose trachea, right carotid and external jugular vein, an osculum is cut in trachea the place ahead in the Thyreoidine below, insert threeway, connecting artificial respirator, is that 280-350ml practices artificial respiration with 20-30 time/min, respiratory quotient 2: 1, tidal volume, regulates respiratory frequency subsequently and autonomous respiration is synchronous; The list of references method
[1], begin to xiphoid-process from presternum, cut skin along midsternal line with 932 type endotherm knifes, passivity is separated flesh layer, hemostasis by ligation; Cut off breastbone with the bone forceps center, passivity is cut pleura, and cutting shoulder is continued to use saline gauze and covered, and machine for chest-opening struts otch, exposes heart; Mention pericardium, cut off along the axle direction, the pericardium sutured on thoracic wall, is become a cradle shape in pericardium the place ahead; From vena femoralis injection 5mg/kg (625u/kg) heparin sodium and 4mg/kg lignocaine; Careful separation aortic root fatty tissue is fixed in aortic root thought-read output with FR100T or FR120T type electromagnetic flowmeter probe; Insert conduit from apex then, connect the YP100 type pressure transducer that is full of heparin-saline, survey left ventricular pressure; It is subcutaneous that pin type electrode thrusts extremity, with ECG6511 type electrocardiograph record II lead electrocardiogram; Pressure transducer is connected with bridge amplifier, the electromagnetic flowmeter probe is connected with MFV-1200 type electromagnetic flowmeter, bridge amplifier, electrocardiograph and electromagnetic flowmeter insert PowerLab 8/e multi-path physiology analyser, with Chart 4.2.3 continuous record and the signal of analyzing collection; Insert No. 14 stomach tubes in order to administration from the oral cavity.
2 detect index
2.1 blood pressure
Before administration and administration after 15,30,60,90,120,180min, measure systolic arterial pressure (SBP, systolic bloodpressure), diastolic pressure (DAP, diastolic blood pressure) and mean arterial pressure (MAP, aterial mean pressure).Be calculated as follows total peripheral vascular resistance (TPVR, total peripheral vascular resistance).
TPVR(kdyn·s·cm
-5)＝MAP×600/CO
2.2 left constant pressure
Before administration and administration after 15,30,60,90,120,180min, measure left constant pressure peak value (LVSP, left ventricularspeak pressure), left chamber EDP (LVEDP, left ventricular diastolic end pressure) and positive and negative the maximum (± LVdP/dt of left constant pressure differential
Max).
2.3 cardiac output
Before administration and after the administration 15,30,60,90,120,180min, measure cardiac output (CO, cardiac output), calculate cardiac index (CI, cardiac index) and the index of fighting (SI, stroke index).
2.4 myocardial contractility and the acting of left chamber
Before administration and administration after 15,30,60,90,120,180min, measure time (t-dP/dtmax), tension time index (TTI that cardiac muscle reaches maximum collapse speed, tension time index), calculate the left ventricle per minute and be work index (LVWIPM, left ventricular work index per minuter) and whenever fight and do work index (LVWIPS, left ventricular work index perstroke).
3 statistical analysis techniques
With Microsoft Excel computation of mean values, standard deviation, relatively t check between organizing.
4 results
4.1 product of the present invention is to the kinemic influence of Beagle dog
Compare with pure water, product 0.11,0.23 of the present invention, 0.45g/kg and FUFANG DANSHEN PIAN 0.076g/kg all do not have obvious influence (table 3) to dog CO, CI and SI.
Table 3. product of the present invention to the kinemic influence of Beagle dog (
N=5)
4.2 product of the present invention is to the influence of Beagle dog heart acting
Compare with pure water, product 0.11,0.23 of the present invention, 0.45g/kg and FUFANG DANSHEN PIAN 0.076g/kg all do not have obvious influence (table 4) to dog LVWIPM and LVWIPS.
Table 4. product of the present invention to the influence of Beagle dog LVWI (
N=5)
4.3 product of the present invention is to the influence of Beagle dog heart rate and myocardial contractility
Compare with pure water, product 0.11,0.23 of the present invention, 0.45g/kg and FUFANG DANSHEN PIAN 0.076g/kg all do not have obvious influence to dog HR and TTI, and 120min can obviously shorten t-dP/dt after product 0.23 of the present invention, the 0.45g/kg administration
Max(table 5).
Table 5. product of the present invention to the influence of Beagle dog heart rate and myocardial contractility (
N=5)
Compare with pure water:
*P＜0.05.
4 discuss
Product of the present invention was given Beagle dog oral administration 5 days, and is not obvious to the influence of cardiac hemodynamics index and cardiac function index, but can shorten t-dP/d 2 hours the time after administration
Tmax, show that product of the present invention has the effect that strengthens myocardial contractility.
(3) product of the present invention forms and hemorheological influence rat suppository
1. research method:
1.1 get 50 of SD rats, body weight 230 ± 34g, male and female half and half, be divided into 5 groups by sex body weight stratified random, the pure water group is given pure water, and other group rats are given compound recipe product mixture 5.4,10.8 of the present invention, 21.6g/kg and FUFANG DANSHEN PIAN 0.26g/kg, gastric infusion respectively, 10ml/kg, administration 7 days.Last administration 30 minutes, the reference literature method prepares the rat suppository model
[1]Rat is pressed the 1.2g/kg intraperitoneal injection of anesthesia with 20% urethanes, lies on the back to be fixed on the Mus plate, separates trachea, inserts plastic bushing; Separate right common carotid artery and left external jugular vein, insert behind the silk thread standby; Silk thread free-end polyethylene tube is inserted left external jugular vein and silk ligature, accurately after the polyethylene tube other end injects the heparin sodium chloride injection, insert right common carotid artery by 50 μ g/kg heparin; Blood flows into polyethylene tube from right common carotid artery and picks up counting; Blocking blood flow in the time of 15 minutes takes out silk thread rapidly and weighs, and calculates thrombus weight.
1.2 prothrombin time (PT) is measured and rheology test
Get above-mentioned anesthetized rat, get blood 4.5ml from posterior vena cava, put and contain in 0.5ml citric acid three sodium solution (0.109mol/L) test tube, mixing takes out 1.0ml, 3000 rev/mins centrifugal 15 minutes, press the operation of prothrombin time test kit description, survey PT; Residue blood is surveyed packed cell volume (HCT) with R80A type hemorheology instrument, respectively at 1,5,30,200s
-1Survey whole blood viscosity (η under the shearing
b), in 200s
-1Survey blood plasma viscosity (η under the shearing
p); With 1s
-1Be low-rate-of-shear (low cutting), 200s
-1Be high shearing (height is cut) that formula is calculated whole blood reduced viscosity (η), whole blood relative viscosity (η calculated as described below
r), erythrocyte rigidity index (IR), deformation index (TK) and aggregate index (RE)
2 results
2.1 product of the present invention is to the influence of rat whole blood viscosity
Compare with pure water, gastric infusion 7 days, product 5.4,10.8 of the present invention, 21.6g/kg and FUFANG DANSHEN PIAN 0.076g/kg can reduce the rat whole blood viscosity; Product dosage of the present invention is 10.8, reduce rat whole blood viscosity significance during 21.6g/kg; FUFANG DANSHEN PIAN reduces the rat whole blood viscosity highly significant meaning (table 2).
Table 2: product of the present invention to the influence of rat whole blood viscosity (
N=10)
Compare with pure water:
*P＜0.05,
*P＜0.01.
2.2 product of the present invention is to the influence of rat plasma viscosity, packed cell volume and whole blood reduced viscosity
Compare with pure water, gastric infusion 7 days, product 10.8 of the present invention, 21.6g/kg and FUFANG DANSHEN PIAN 0.076g/kg have the effect that reduces the rat plasma viscosity; Reduce rat whole blood height slightly during product 21.6g/kg of the present invention and cut reduced viscosity; FUFANG DANSHEN PIAN can reduce rat whole blood height and cut the low reduced viscosity (table 3) of cutting of reduced viscosity whole blood.
3: product of the present invention to the influence of rat plasma viscosity, packed cell volume and whole blood reduced viscosity (
N=10)
Compare with pure water:
*P＜0.05,
*P＜0.01.
2.3 product of the present invention is to the exponential influence of rat erythrocyte
Compare with pure water, gastric infusion 7 days, product 5.4,10.8 of the present invention, 21.6g/kg all do not have obviously influence to rat erythrocyte rigidity index (IR), deformation index (TK) and aggregate index (RE); FUFANG DANSHEN PIAN 0.076g/kg obviously reduces rat erythrocyte RE, increases IR and TK (table 5).
Table 5: product of the present invention to the influence of rat erythrocyte IR, TK and RE (
N=10)
Compare with pure water:
*P＜0.05.
3 conclusions
Product of the present invention is given rat oral gavage 7 days, but can slightly reduce whole blood viscosity, blood plasma viscosity and whole blood reduced viscosity, and erythrocyte IR, TK and RE are not had obvious influence.The compound Caulis Seu Folium Euonymi Fortunei mixture reduces the effect of blood viscosity, helps the blood supply of body tissue.
Result of the test to sum up: product of the present invention has the effect that resists myocardial ischemia, ischemic myocardium is had protective effect, and myocardial damage is alleviated, and product of the present invention has the effect that strengthens myocardial contractility.Product of the present invention can slightly reduce whole blood viscosity, blood plasma viscosity and whole blood reduced viscosity, has the effect of treatment coronary heart disease, ischemic heart desease.
Clinical observation:
With product of the present invention 120 routine chest arthralgia precordial pain syndrome patients are treated, total effective rate 78.33% as a result; With product of the present invention ischemic heart desease 114 examples are observed, the result shows product of the present invention relief of symptoms effectively, improve electrocardiogram, total effective rate 90.4%, whole blood contrast viscosity, plasma viscosity, erythrocyte electrophoresis, ESR etc. all have clear improvement before and after the treatment.
Process of clinical application does not see that toxic and side effects takes place.
Two, embodiment
Embodiment 1.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 10 Radix Ginseng Rubra 10g Caulis Seu Folium Euonymi Fortunei 10g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct collecting decoction 2 hours at every turn, filter, it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, puts cold, the ethanol that adds 2 times of amounts, the limit edged stirs evenly, and leaves standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, and reclaim ethanol, medicinal liquid mixes with filtrate (B), and it is the clear paste of 1.3-1.35 that simmer down to is surveyed relative density for 70 ℃, 80 ℃ of drying under reduced pressure, pulverize, add right amount of auxiliary materials, make tablet.
Embodiment 2.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 400 Radix Ginseng Rubra 80g Caulis Seu Folium Euonymi Fortunei 1000g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct collecting decoction 2 hours at every turn, filter, it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, puts cold, the ethanol that adds 2 times of amounts, the limit edged stirs evenly, and leaves standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, and reclaim ethanol, medicinal liquid mixes with filtrate (B), and 70 ℃ of simmer down tos to survey relative density be the clear paste of 1.3-1.35,80 ℃ of drying under reduced pressure, pulverize, add right amount of auxiliary materials, make granule.
Embodiment 3.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 200 Radix Ginseng Rubra 40g Caulis Seu Folium Euonymi Fortunei 500g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct 2 hours at every turn, collecting decoction, filter, it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, puts cold, the ethanol that adds 2 times of amounts, the limit edged stirs evenly, and leaves standstill more than 48 hours, filters, filtrate and above-mentioned solution A merge, reclaim ethanol, medicinal liquid mixes with filtrate (B), and 70 ℃ of surveys of simmer down to relative density is the clear paste of 1.2-1.35,80 ℃ of drying under reduced pressure, pulverize, add right amount of auxiliary materials, mixing, be divided in Capsules or be sealed in the soft capsule material, packing promptly gets hard capsule product or soft capsule product.
Embodiment 4.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 300 Radix Ginseng Rubra 70g Caulis Seu Folium Euonymi Fortunei 900g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali, decoct with water secondary, the each decoction 2 hours, collecting decoction filters, it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, add the ethanol of 2 times of amounts, the limit edged stirs evenly, leave standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, and reclaim ethanol, medicinal liquid mixes with filtrate (B), and 70 ℃ of simmer down tos to survey relative density be the clear paste of 1.2-1.35, behind glyceryl monostearate heating and melting mixing, splash in the not miscible condensed fluid, shrink condensation and make sphere or the spheric preparation of class, packing promptly gets drop pill.
Embodiment 5.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 200 Radix Ginseng Rubra 40g Caulis Seu Folium Euonymi Fortunei 500g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct 2 hours at every turn, collecting decoction, filter, it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, puts cold, the ethanol that adds 2 times of amounts, the limit edged stirs evenly, and leaves standstill more than 48 hours, filters, filtrate and above-mentioned solution A merge, reclaim ethanol, medicinal liquid mixes with filtrate (B), and 70 ℃ of surveys of simmer down to relative density is the clear paste of 1.2-1.35,80 ℃ of drying under reduced pressure, pulverize, add right amount of auxiliary materials, mixing, briquetting or adorn tea bag or fry in shallow oil in the bag then, packing promptly gets medicinal tea.
Embodiment 6.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 250 Radix Ginseng Rubra 30g Caulis Seu Folium Euonymi Fortunei 500g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct 2 hours at every turn, collecting decoction filters, and it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, add the ethanol of 2 times of amounts, the limit edged stirs evenly, leave standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, reclaim ethanol, add water in right amount mixing, add 50% an amount of Ovum Gallus domesticus album solution, stir evenly, boil, filter, filtrate and above-mentioned liquor B merge, and add an amount of sucrose, boil and make dissolving, add right amount of auxiliary materials again, boil, filter, add water to ormal weight, stir evenly, fill promptly gets syrup.
Embodiment 7.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 200 Radix Ginseng Rubra 20g Caulis Seu Folium Euonymi Fortunei 500g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct 2 hours at every turn, collecting decoction filters, and it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, add the ethanol of 2 times of amounts, the limit edged stirs evenly, leave standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, reclaim ethanol, and to survey relative density for 70 ℃ with filtrate (B) simmer down to be the clear paste of 1.2-1.35, add refined honey and receive cream, add an amount of antiseptic, packing promptly gets soft extract.
Embodiment 8.
Take by weighing the raw material of Chinese medicine of following portions by weight: the Radix Astragali 200 Radix Ginseng Rubra 40g Caulis Seu Folium Euonymi Fortunei 600g
Method for making: Radix Ginseng Rubra extracts three times with 65% alcohol heating reflux, and each 2 hours, merge extractive liquid, filtered, and (A) is standby for filtrate; Medicinal residues decoct with water three times, decoct 1.5 hours at every turn, and collecting decoction filters, and it is 1.04～1.08 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, leave standstill more than 48 hours, filter, and (B) is standby for filtrate; Caulis Seu Folium Euonymi Fortunei, the Radix Astragali decoct with water secondary, decoct 2 hours at every turn, collecting decoction filters, and it is 1.12～1.16 (60 ℃ of surveys) that filtrate is concentrated into relative density, put coldly, add the ethanol of 2 times of amounts, the limit edged stirs evenly, leave standstill more than 48 hours, filter, filtrate and above-mentioned solution A merge, reclaim ethanol, and simmer down to survey relative density for 70 ℃ be the clear paste of 1.2-1.35, press the method for making of mixture, add filtrate (B), add right amount of auxiliary materials, make mixture.
Embodiment 9.
Take by weighing the raw material of Chinese medicine of following portions by weight: Radix Astragali 10g Radix Ginseng Rubra 10g Caulis Seu Folium Euonymi Fortunei 10g.
Method for making: get Radix Ginseng Rubra, the Radix Astragali, Caulis Seu Folium Euonymi Fortunei, powder is beaten in oven dry respectively, and three's fine powder is mixed, and mixing adds an amount of adjuvant, divides the bag of packing into, promptly gets powder.
The described adjuvant of the foregoing description is the adjuvant product that the relevant administration section's regulation of country can be applied to food, pharmaceutical production, comprises the food additive kind that meets national regulation and other the complementary composition except that raw material.
Substantive distinguishing features of the present invention and significant progress are:
1, the present invention is in clinical practice for many years, by a large amount of clinical observation cases, use for reference simultaneously the achievement of modern pharmacology research, invented out a kind of pharmaceutical composition in the new purposes of the medicine of preparation treatment coronary heart disease, enlarged the clinical application range of Chinese medicine preparation product.
2, the present invention's curative effect in clinical practice is obvious, the application and popularization value height, and for improving the patients with coronary artery disease clinical symptoms, the existence quality of life effect that improves patient is remarkable, and long-term taking is not found toxic and side effect.
Claims (1)
1. the application of pharmaceutical composition in preparation treatment medicaments for coronary disease, wherein the weight proportion of each flavour of a drug of said composition is as follows:
10～80 parts of Radix Ginseng Rubra, 10～400 parts of the Radixs Astragali, 10～1000 parts of Caulis Seu Folium Euonymi Fortuneis.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102357115A (en) * | 2011-10-12 | 2012-02-22 | 广西中医学院制药厂 | Sugar-free compound wintercreeper mixture and production method thereof |
| CN108498565A (en) * | 2018-05-23 | 2018-09-07 | 广西中医药大学 | A kind of Fufang Fufangteng soft capsule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1432393A (en) * | 2003-03-06 | 2003-07-30 | 凌沛学 | Chinese medicine prepn for treating coronary heart disease and angina pectoris and its prepn |
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2010
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1432393A (en) * | 2003-03-06 | 2003-07-30 | 凌沛学 | Chinese medicine prepn for treating coronary heart disease and angina pectoris and its prepn |
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| Title |
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| 《中华人民共和国药典（2005年版一部）》 20050131 国家药典委员会 复方扶芳藤合剂 化学工业出版社 , 1 * |
| 《广西中医药》 20000620 邓家刚 复方扶芳藤合剂异病同治举隅 第25卷, 第3期 2 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102357115A (en) * | 2011-10-12 | 2012-02-22 | 广西中医学院制药厂 | Sugar-free compound wintercreeper mixture and production method thereof |
| CN108498565A (en) * | 2018-05-23 | 2018-09-07 | 广西中医药大学 | A kind of Fufang Fufangteng soft capsule and preparation method thereof |
| CN108498565B (en) * | 2018-05-23 | 2020-12-29 | 广西中医药大学 | Compound wintercreeper soft capsule and preparation method thereof |
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