CN1291735C - Chinese medicine drippling pill preparation for promoting blood circulation and removing blood stasis, promoting Qi circulation and rilieving pain - Google Patents
Chinese medicine drippling pill preparation for promoting blood circulation and removing blood stasis, promoting Qi circulation and rilieving pain Download PDFInfo
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Abstract
The present invention relates to a novel Chinese medicine preparation which is a xinkeshu dropping-pill preparation. The dropping-pill preparation is prepared by using novel technology which comprises the following steps: step a, haws, pueraria roots and notoginseng are extracted by ethanol, the extracted is filtrated, and the filtered liquid is used for spare use; step b, red sage roots are extracted by the ethanol or water, and the extracted liquid is filtrated to obtain filtered liquid; step c, the filtered liquid obtained in the step b and the filtered liquid obtained in the step a are merged, concentrated and extracted by the mixed solvent of acetate or ethanol and acetate, and extracted liquid is concentrated to obtain thick paste or dried powder; step d, aucklandia roots are pulverized, the ethanol is used as a solvent for immersion and diacolation, and diacolation liquid is used for recovering the ethanol to be concentrated into thick paste; step e, the dried powder or the thick paste obtained in the step c is added into the molten polyethylene glycol, the thick paste obtained in the step d is added, the medical liquid is placed into a material storing tank of a dropping-pill machine, and the medical liquid is made into dropping pills by the dropping-pill machine.
Description
Technical field:
The present invention relates to a kind of Chinese medicine preparation, particularly a kind of blood circulation promoting and blood stasis dispelling, the Chinese medicine dripping pills preparation of promoting the circulation of QI to relieve pain, this dropping pill formulation are to adopt new prepared.
Background technology:
XINKESHU PIAN be Shandong China Wo Medicine Co according to the seventies well-known doctor's proved recipe develop voluntarily; now record in the 16 (protection fascicle) the 24th page of " Drug Standard of Ministry of Public Health of the Peoples Republic of China " Chinese traditional patent formulation preparation, XINKESHU PIAN is national essential drug kind, national medical insurance kind, national Chinese medicine protection kind.XINKESHU PIAN is made up of Radix Salviae Miltiorrhizae, Radix Puerariae, Fructus Crataegi, Radix Notoginseng, the Radix Aucklandiae, has blood circulation promoting and blood stasis dispelling, the effect of promoting the circulation of QI to relieve pain.Diseases such as clinical uncomfortable in chest, the angina pectoris that is used for that qi stagnation blood stasis type coronary heart disease causes, hypertension, dizziness, headache, neck pain and arrhythmia, hyperlipidemia.This product determined curative effect, toxic and side effects is few, is subjected to the welcome of vast patients with coronary heart disease deeply.
Along with the continuous development of science and technology and improving constantly of new drug development level, the continuous application of new theory, new technique, new technology, new equipment, XINKESHU PIAN is not in full conformity with the requirement of the modernization of Chinese medicine.Mainly direct pulverizing of part crude drug is used as medicine in the side of showing, dose is big, and bioavailability is low, and the drug effect performance is slower.For overcoming the deficiency of XINKESHU PIAN, preparation reaches the curative effect height, dosage is little, toxic and side effects is little in line with making, accumulating portably uses purpose easily, and on the prescription basis of XINKESHU PIAN, the present invention is improved to drops through technological transformation with XINKESHU PIAN.But heart drop pills preparation of the present invention, drug absorption is fast, and produce effects is rapid, the bioavailability height, preparation technology is simple, and dose is few, and very suitable patients with coronary heart disease medication selects for use drops can satisfy the demand of patients with coronary heart disease better.
Summary of the invention:
The present invention has carried out technological transformation to XINKESHU PIAN, by being extracted with new technology, Chinese medicine of the five flavours such as Radix Salviae Miltiorrhizae, Radix Puerariae, Fructus Crataegi, Radix Notoginseng, the Radix Aucklandiae obtain new extract, be active constituents of medicine further again with this extract, the new pharmaceutical preparation of making: dropping pill formulation.
Its prescription of dropping pill formulation of the present invention is composed as follows:
Radix Puerariae 500～800g, Fructus Crataegi 400～800g, Radix Salviae Miltiorrhizae 400～800g, Radix Notoginseng 20～60g, the Radix Aucklandiae 20～60g.
Preferably:
Radix Puerariae 600～800g, Fructus Crataegi 500～700g, Radix Salviae Miltiorrhizae 500～700g, Radix Notoginseng 30～50g, the Radix Aucklandiae 30～50g.
More preferably:
Radix Puerariae 600g Fructus Crataegi 600g Radix Salviae Miltiorrhizae 600g Radix Notoginseng 40g Radix Aucklandiae 40g
More than the prescription composition can be made pharmaceutical preparation: 10000 of drop pill.
The present invention also comprises, Chinese medicine extract made from above prescription and preparation method thereof.
The preparation method of Chinese medicine extract of the present invention may further comprise the steps:
Get Radix Salviae Miltiorrhizae, Radix Puerariae, Fructus Crataegi, Radix Notoginseng, Radix Aucklandiae Chinese medicine of the five flavours material,
Step a: wherein Fructus Crataegi, Radix Puerariae, Radix Notoginseng are used ethanol extraction, extracting liquid filtering, filtrate for later use;
Step b: Radix Salviae Miltiorrhizae ethanol or water extraction, extracting solution filter filtrate;
The filtrate that step c: step b and step a obtain merges, and concentrates, and with the mixed extractant solvent of ethyl acetate or ethanol and ethyl acetate, extract concentrates, and gets thick paste or dried powder;
Steps d: the Radix Aucklandiae is pulverized and is made solvent with ethanol, soaks, and percolation, percolate reclaims ethanol, is condensed into thick paste;
Preferably can adopt following steps:
Step a: Fructus Crataegi, Radix Puerariae, Radix Notoginseng, measure 40～80% alcohol reflux 2 times for 3～10 times with each medical material, 1～3 hour for the first time, 1～3 hour for the second time, merge alcohol extract, reclaim ethanol, filtration, filtrate for later use;
Step b: Radix Salviae Miltiorrhizae extracts three times, adds 60～95% alcohol refluxs 1～3 hour of 3～15 times of amounts of medical material for the first time, filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add for the second time 20～80% alcohol refluxs 1～3 hour of 3～15 times of amounts, filter, reclaim ethanol; The water that adds 3～15 times of amounts of medical material for the third time refluxed 1～3 hour, filtered merging filtrate;
Step c: merge with the standby filtrate of step a, being evaporated to relative density jointly is the clear paste of 1.06-1.12 (80 ℃ of surveys), with 10～60% alcoholic acid ethyl acetate extractions of the ethyl acetate of equimultiple or equimultiple 3～6 times, combining extraction liquid, and concentrating under reduced pressure becomes thick paste, or with thick paste in 60～80 ℃ of dryings 8 hours, pulverize, cross 80 mesh sieves, get dried powder;
Steps d: Radix Aucklandiae powder is broken into coarse powder, according to " percolation is made solvent with 60～95% ethanol under Chinese pharmacopoeia appendix 20 fluid extracts of version in 2000 and the extractum item, soaks after 24 hours, and percolation, percolate reclaim the ethanol concentrating under reduced pressure and become thick paste;
Thick paste that step c and steps d obtain or dry powder are exactly extract of the present invention, and this extract can be aqueous extractum, also can be exsiccant extractum or powder, decide according to the needs of made preparation.
The present invention comprises that also said preparation comprises any dosage form of taking, as tablet, capsule, granule, oral liquid, pill, drop pill etc., most preferably drop pill with the Chinese medicine preparation of Chinese medicine extract of the present invention as the active constituents of medicine preparation.
Chinese medicine preparation of the present invention can add the medicine acceptable carrier as required by the technology preparation of galenic pharmacy routine during preparation.
Drop pill of the present invention can prepare by the following method:
Thick paste or dried powder that step c in the above method for preparing extractive is obtained add in the mixture of fused Macrogol 4000 or polyethylene glycol 6000 or Macrogol 4000 and polyethylene glycol 6000, add the thick paste that steps d obtains again, stir evenly, medicinal liquid is put in the drop pill machine material-storage jar, make drop pill with the drop pill machine, promptly.Preferably thick paste that step c is obtained or dried powder add in the mixture of fused an amount of Macrogol 4000 or polyethylene glycol 6000 or Macrogol 4000 and polyethylene glycol 6000, add the thick paste that the Radix Aucklandiae extracts again, stir evenly, medicinal liquid is put in the drop pill machine material-storage jar, insulation (80～85 ℃), splash into and be cooled in 5～10 ℃ of dimethicones with the speed of dripping of water dropper with 30～60 droplets/minute, with refrigerative drop pill, absorb coolant, drying, make 10000, promptly.
Dropping pill formulation through above method preparation, has tangible advantage, can remove most of impurity and keep the effective ingredient of each flavour of a drug to greatest extent by selected extraction, purification, technology such as refining, make the dried cream yield of medical material reach 5.0～6.5%, taking under the constant situation of crude drug amount, the drug administration amount reduces, active constituent content improves, by to using the drug extract that this technology makes and the pharmacodynamics test contrast of dropping pill formulation of making and XINKESHU PIAN agent, the result shows that the drug effect of dropping pill formulation is better.
Below by pharmacodynamic experiment data declaration beneficial effect of the present invention.
The medicine that the present invention uses prepares as preferable methods among the embodiment, but called after heart drop pills,
(1) but heart drop pills function of resisting myocardial ischemia research
Medicine and reagent
Medicine and reagent: but heart drop pills, lot number: 031011; The positive control drug XINKESHU PIAN, lot number 030912.Provide by Shandong China Wo Medicine Co, be mixed with desired concn with normal saline with preceding.Lignocaine, lot number 20030708, Beijing Yimin Pharmaceutical Co., Ltd. produces; Pentobarbital sodium, lot number 020919, the import packing of Beijing chemical reagents corporation; Red tetrazolium (TTC), lot number 1412B41, AMRESCO company product; Heparin sodium injection, lot number 030628, Chinese changzhou biochemical thousand red pharmaceutical Co. Ltds produce.Lactic acid dehydrogenase (LDH) test kit lot number 130071, creatine kinase (CK) test kit lot number 090143, Beijing Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd. produces.
Animal: the hybrid dog, the male and female dual-purpose, body weight: 17.5 ± 2.2kg, the first edge laboratory animal of virtue plant provides by Beijing.
Instrument: SC-3 type electric pulmotor (Shanghai Medical Equipment Factory); MFV-3200 type electromagnetic flowmeter (Japanese photoelectricity product); MP150 type physiograph (U.S. BIOPAC company); RMP6008 physiograph (Japanese photoelectricity product); R80 type blood viscosity instrument (Beijing Steellex Scientific Instrument Company).
Test method: the hybrid dog is divided into 5 groups at random, is respectively model group, positive controls (positive reference substance 160mg/kg), heavy dose of group (being subjected to test product 22mg/kg), middle dosage group (being subjected to test product 11mg/kg), small dose group (being subjected to test product 5.5mg/kg).Animal pentobarbital sodium 30mg/kg intravenous injection anesthesia separates left carotid, and intubate connects the pressure transducer recording blood pressure.Tracheal intubation is carried out assisted respiartion.The 4th intercostal is opened breast along the left side, seam pericardium bed.Separate aortic arch, place the electromagnetic flowmeter probe, measure cardiac output.Apex of the heart intubate connects pressure transducer, measures intraventricular pressure.Seam is put 16 epicardial leads of leading and is connected ecg amplifier, record visceral pericardium electrocardio.The abdominal part opening separates duodenum, is equipped with administrable.After every index that writes down is stablized 15min, adopt two steps ligation method ligation arteria coronaria left anterior descending branch, and administration in 5 minutes after formal ligation, model group is given the normal saline with equivalent.Respectively before ligation, ligation at once, 5,10,15,30,45,60,90,120,150,180min record visceral pericardium electrocardio calculates above each mapping point ST section constantly and raises total millivolt (mV) number and represent degree of myocardial ischemia, counts the ST section and raises to count greater than the mapping of 2mV and represent the myocardial ischemia scope.Respectively at 180min time point heart extracting blood before the pre-bundle and after the ligation, measure LDH and CK content in whole blood viscosity and the serum.It is dirty to core during off-test, on average is cut into five from the apex of the heart to ligation point, and 1%TTC dyeing is taken pictures, and picture is imported computer, calculates the ratio of infarct size and cutting cardiac muscular tissue area.
The result
By table 1-2 as seen, after the ligation of model group animal, electrocardio ST section is obviously raised; Tend towards stability by 5 minutes beginning animal cardiac muscle degree of ischemia after the visible ligation of table 1-1 simultaneously; In addition, the serology result confirm before the ligation with ligation after 3 hours, LDH and CK level obviously raise in the animal serum.Above result illustrates that all the dog myocardial infarction and ischemia model forms, and ligation after 5 minutes ischemia tend towards stability, can administration.
After the positive control drug 160mg/kg administration 10 minutes (be after the ligation 15 minutes), the scope of myocardial ischemia (table 1-1) begins to dwindle, simultaneously the order of severity of ischemia (table 1-2) also decreases, and wherein 30 minutes time point The above results and model group relatively have significant difference after the ligation.Cardiac muscle coloration result (table 1-3) and serology result (show 1-4, confirm also that 1-5) positive control drug can obviously alleviate the myocardial damage that coronary ligation causes.
After being subjected to reagent 22mg/kg administration, LDH, CK level and model group are approaching in the scope of each time point myocardial ischemia, ischemic myocardium ratio and the serum, and the ischemia order of severity and model group alleviate more to some extent.After being subjected to reagent 11mg/kg administration, as seen 10 minutes (after the ligation 15 minutes) beginning behind the self administration of medication, the scope and the order of severity of animal cardiac muscle ischemia all decrease, and after the ligation 30,60,120 minutes the time ischemia scope and model group significant difference is relatively arranged, after the ligation 10,30,60,120 minutes the time ischemia order of severity and model group significant difference is relatively arranged, ischemic myocardium ratio and serology result and model group more also have significant difference.Similar to the heavy dose group, be subjected to reagent 5.5mg/kg administration after, myocardial ischemia scope and model group are approaching, other index (the myocardial ischemia order of severity, ischemic myocardium ratio, Serum LDH, CK level) and model group more all decrease.
Electrocardio ST section presentation of results is subjected to reagent 11mg/kg and positive control drug 160mg/kg relatively, and the degree and the scope of each time point myocardial ischemia have notable difference.Among whole myocardium coloration result and the serology result, also has notable difference between two groups.
Conclusion
But heart drop pills 11mg/kg duodenal administration can obviously alleviate the dog acute myocardial ischemia damage that coronary ligation causes, and this effect is better than the effect after the positive control drug 160mg/kg administration.
But table 1-1. heart drop pills is to the influence of anesthetized dog myocardial ischemia scope (N-ST) (X ± SD)
| Dosage (mg/kg) | Number of animals | Minute (minute) | |||||||||||
| At once | 5 | 10 | 15 | 30 | 45 | 60 | 90 | 120 | 150 | 180 | |||
| Dosage low dose in the positive heavy dose of model | -- 160 22 11 5.5 | 6 5 5 5 5 | 13.3±2.6 14.4±1.1 12.0±7.8 12.0±2.9 14.6±4.6 | 14.8±1.5 14.4±1.5 13.4±0.9 14.0±1.6 15.2±0.8 | 14.3±1.5 15.0±1.2 13.6±0.9 12.6±3.4 15.0±1.7 | 14.3±1.7 13.0±2.5 12.0±0.0 12.4±3.6 14.2±2.0 | 15.3±1.5 12.0±3.3 * 10.6±0.5 10.4±4.2 * 14.6±1.7 | 15.5±1.0 15.2±0.8 11.6±0.5 12.0±2.8 14.4±1.1 | 14.8±1.5 14.2±1.8 11.8±0.4 11.6±2.5 * 14.8±1.3 | 15.0±1.2 12.4±3.4 12.0±0.0 12.0±2.5 14.6±1.1 | 15.8±0.5 12.4±3.0 10.4±1.3 10.0±3.2 * 15.2±1.3 | 16.0±0.0 11.6±4.4 10.8±0.5 12.2±2.6 15.0±1.2 | 16.0±0.0 9.6±5.5 9.0±0.0 9.0±4.7 14.8±1.3 |
Corresponding result constantly with model group compares,
*P＜0.05; But dosage, the corresponding result constantly with positive group of heavy dose of group compare P＜0.05 in the heart drop pills.
But the influence that table 1-2. heart drop pills is raised epicardial electrogram ST section due to the anesthetized dog myocardial ischemia (X ± SD, mV)
| Dosage (mg/kg) | Number of animals | Minute (minute) | |||||||||||
| At once | 5 | 10 | 15 | 30 | 45 | 60 | 90 | 120 | 150 | 180 | |||
| Dosage low dose in the positive heavy dose of model | -- 160 22 11 5.5 | 6 5 5 5 5 | 6.9±3.67 5.1±0.98 3.7±4.27 3.5±1.78 3.7±2.17 | 11.7±5.95 6.4±1.71 4.8±2.71 5.1±1.90 6.3±2.33 | 11.4±5.98 6.6±1.53 4.0±3.06 4.2±2.02 * 6.1±2.32 | 10.9±6.83 5.2±2.95 4.5±2.20 4.7±2.10 5.5±2.12 | 10.1±5.26 4.1±2.73 * 2.6±2.20 3.1±3.39 * 6.2±2.98 | 10.8±6.01 4.9±1.14 3.5±2.41 4.1±2.38 6.6±3.08 | 10.7±5.83 4.4±2.31 3.3±2.31 3.9±1.53 * 7.0±3.41 | 11.0±5.72 4.0±3.50 3.1±2.61 3.7±1.67 6.9±2.88 | 12.0±4.35 4.5±4.33 2.2±2.88 2.8±1.84 * 6.5±2.36 | 14.7±3.22 4.3±4.49 3.3±3.00 3.8±1.76 5.9±1.77 | 14.3±4.00 3.6±4.68 3.0±2.50 3.2±2.76 6.3±3.06 |
Corresponding result constantly with model group compares,
*P＜0.05; But dosage, the corresponding result constantly with positive group of heavy dose of group compare P＜0.05 in the heart drop pills.
But table 1-3. heart drop pills is to the influence of anesthetized dog coronary ligation myocardial infarct size after 3 hours (X ± SD)
| Dosage (mg/kg) | Number of animals | Ischemia scope (%) | |
| Dosage low dose in the positive heavy dose of model | -- 160 22 11 5.5 | 6 5 5 5 5 | 0.035±0.013 0.014±0.011 * 0.011±0.046 0.012±0.005 * 0.020±0.020 |
Compare with model group,
*P＜0.05; But dosage, heavy dose of group are compared P＜0.05 with positive group in the heart drop pills
But table 1-4. heart drop pills is to the influence of LDH level in the serum before and after the anesthetized dog coronary ligation (X ± SD)
| Number of animals | Dosage (mg/kg) | Before the ligation | After the ligation 3 hours | Difference before and after the ligation | |
| Dosage low dose in the positive heavy dose of model | 6 5 5 5 5 | -- 160 22 11 5.5 | 74.8±23.6 76.8±11.5 83.0±50.9 72.2±22.7 79.2±26.3 | 161.3±21.4 126.8±23.6 * 115.4±59.8 122.0±14.0 * 127.2±26.4 | 86.5±23.6 50.0±18.1 * 35.4±24.0 45.8±20.1 * 51.0±30.3 |
Compare with model group,
*P＜0.05; But dosage, heavy dose of group are compared P＜0.05 with positive group in the heart drop pills
But table 1-5. heart drop pills is to the influence of CK level in the serum before and after the anesthetized dog coronary ligation (X ± SD)
| Number of animals | Dosage (mg/kg) | Before the ligation | After the ligation 3 hours | Difference before and after the ligation | |
| Dosage low dose in the positive heavy dose of model | 6 5 5 5 5 | -- 160 22 11 5.5 | 302.8±143.5 324.4±125.2 387.2±95.6 403.8±88.9 427.6±121.1 | 1571.5±741.9 766.4±257.6 * 675.9±237.5 786.0±207.9 * 772.4±391.8 | 1268.7±753.7 442.0±241.7 * 288.7±147.1 382.2±167.2 * 460.8±210.3 |
Compare with model group,
*P＜0.05; But dosage, heavy dose of group are compared P＜0.05 with positive group in the heart drop pills
(2) but heart drop pills is treated ARR experimental study
Material and method
Medicine and reagent: but heart drop pills, lot number: 031011; The positive control drug XINKESHU PIAN, lot number 030912.Provide by Shandong China Wo Medicine Co, be mixed with desired concn with normal saline with preceding.Pentobarbital sodium, lot number 030919, Beijing chemical reagents corporation;
Heparin sodium injection, lot number 030128, Chinese changzhou biochemical thousand red pharmaceutical factories produce.
Propylthiouracil: morning sunlight pharmaceutical factory of The 2nd Army Medical College produces, lot number: 031103.
Aconitine is produced by Merck company
Urethanes: China Medicine (Group) Shanghai Chemical Reagent Co.,, lot number: 020342.
Pentobarbital: import packing, Shanghai chemical reagent purchasing and supply station packing.Lot number: 021122.
Animal
The Wistar rat, Shandong Traditional Chinese Medicine University's animal center provides.
Instrument
MP150 type physiograph (U.S. BIOPAC company); Rat blood pressure analyzer Tian Jinjin defends Electronics Factory and produces.Kenz ECG103 electrocardiograph, Japan produces.
Test method and result
1, but heart drop pills is to the influence of ischemic arrhythmia
Get 60 of male rats, body weight 250 ± 20g is with 20% urethanes 1g/kg, behind the intraperitoneal injection of anesthesia, it is fixing that rat faces upward the position, record II lead electrocardiogram, reject the abnormal rat of electrocardiogram, cut off the 3-4 rib, open breast and cut off pericardium along left border of sternum, expose heart, the ligation of left anterior descending coronary artery root threading, promptly prop up chamber, a 2mm place ligation coronary artery left side below pulmonary conus and left auricle root, and heart is put back to the thoracic cavity, overstock the thoracic cavity gently, extrude gas in the thoracic cavity.Measuring the animal electrocardiogram after 15 minutes in ligation then, is observation index with ∑ S-T, as myocardial ischemia electrocardiogram after the ligation.Each rat difference duodenal administration once then, XINKESHU PIAN low dose, middle dosage, heavy dose, XINKESHU PIAN and normal saline, administration volume are 0.5ml/100g, different time sections is measured electrocardiogram, Electrocardiographic difference after 5h animal electrocardiogram and the ligation after the record analysis administration after administration; Raise as the arrhythmia index to occur the ST section on the electrocardiogram, result of the test sees Table 2-1,
But table 2-1 heart drop pills is to (the X ± SD) of the Electrocardiographic influence of acute myocardial ischemia due to the rat coronary ligation
| Group | Dosage (mg/kg) | ∑ S-T (mv) before the medicine | ∑ S-T (mv) behind the medicine | Before the medicine-medicine after (mv) |
| The heavy dose of group of dosage group XINKESHU PIAN group in the normal saline small dose group | Isometric(al) 5.5 11 22 160 | 9.21±2.34 9.23±3.21 8.98±2.76 9.43±3.27 9.23±2.46 | 9.22±3.11 8.22±2.47 6.61±2.34 ※ 5.89±2.13 ※※ 6.56±3.01 ※ | -0.02±0.02 1.02±0.52 ※※ 2.38±0.54 ※※ 3.54±0.89 ※※ 2.67±0.65 ※※ |
Compare ※ p＜0.05, ※ ※ p＜0.01 with the normal saline group; But dosage group and XINKESHU PIAN group compare P＜0.05 in the heart drop pills, but the heavy dose of group of heart drop pills compares P＜0.01 with the XINKESHU PIAN group.
From test as can be seen: XINKESHU PIAN and drop pill all can obviously reduce raising of rat electrocardiogram S-T, and the reduction amplitude meets dose-effect relationship, but but heart drop pills effect is better than XINKESHU PIAN, be significant difference.
2, but heart drop pills brings out the influence of rat ventricular to aconitine
Get 50 male and female half and half of rat, body weight 220-250g is divided into 5 groups at random.But continuous irrigation stomach heart drop pills low dose, middle dosage, heavy dose and XINKESHU PIAN then, successive administration 7 days.After the last administration 1 hour, lumbar injection urethane 1g/kg, it is fixing that rat faces upward the position, normal ECG is described, record II lead electrocardiogram is rejected the abnormal rat of electrocardiogram, and sublingual vein has pushed away aconitine 20ug/kg in 10 seconds again, observe the time of rat ventricular appearance and the time that arrhythmia is kept immediately, result of the test sees Table 2.
But table 2-2, heart drop pills bring out the influence (X ± SD) of rat ventricular to aconitine
| Group | Dosage (mg/kg) | Arrhythmia time of occurrence (min) | The arrhythmia persistent period (min) |
| The heavy dose of group of dosage group XINKESHU PIAN group in the normal saline group small dose group | -- 5.5 11 22 160 | 1.86±0.87 2.55±1.11 3.54±1.43 ※※ 4.38±1.54 ※※ 2.76±1.07 ※ | 132±24 113±25 109±19 ※ 98±16 ※※ 113±19 ※ |
Compare ※ p＜0.05, ※ ※ p＜0.01 with the normal saline group; But dosage group and XINKESHU PIAN group compare P＜0.05 in the heart drop pills, but the heavy dose of group of heart drop pills compares P＜0.01 with the XINKESHU PIAN group.
From test as can be seen: XINKESHU PIAN and drop pill can both postpone the time that arrhythmia occurs, and shorten the time that arrhythmia is kept, and have tangible antiarrhythmic effect, but but heart drop pills effect is better than tablet, have significant difference.
Conclusion:
But heart drop pills can obviously improve the myocardial ischemia degree of arrhythmia; Obviously postpone the arrhythmia time of occurrence that aconitine causes, shorten aconitine institute's proarrhythmia persistent period.But heart drop pills arrhythmia effect is better than XINKESHU PIAN, has significant difference
(3) but heart drop pills is treated hypertensive experimental data and study
Material and reagent
But heart drop pills, Shandong China Wo Medicine Co, lot number: 031011
Animal dosage is determined: drop pill is made into 3%, 6%, 12% concentration respectively with distilled water, and the administration volume is 1ml/kg, then low dose of 5 times of being equivalent to people's consumption, and 10 times of middle dosage behaviour consumption, heavy dose is 20 times of people's consumption.The normal saline group is irritated the isometric normal saline of stomach.
XINKESHU PIAN: provide lot number by Shandong China Wo Medicine Co: 030912
Lignocaine, lot number 031108, Beijing Yimin Pharmaceutical Co., Ltd. produces;
Pentobarbital sodium, lot number 030919, Beijing chemical reagents corporation;
Urethanes: China Medicine (Group) Shanghai Chemical Reagent Co.,, lot number: 020342.
Animal
The Wistar rat, Shandong Traditional Chinese Medicine University's animal center provides.
Instrument
MP150 type physiograph (U.S. BIOPAC company); RMP6008 physiograph (Japanese photoelectricity product).
Test method and result
Get 60 of healthy male rats, body weight 250 ± 20g, lumbar injection pentobarbital sodium 40mg/kg, be fixed on the big rat holder, cut off dorsal body setae, iodine tincture and alcohol disinfecting, cover ambut towel,, cut skin downwards from the rib lower edge in left of spine, peel off muscle, expose kidney, separate renal artery, ligation renal artery after putting a diameter 0.2mm thin copper wire on the renal artery is extracted copper wire out, skin suture, put back to mouse cage after the sterilization, this is for forming two kidneys, one folder renal hypertension.Rat blood pressure is measured with the rat blood pressure analyzer in the back all around, surveys twice continuously for every, with twice meansigma methods as this Mus blood pressure.Be higher than the rat of 25kpa as Hypertensive Rats with systolic pressure, with Hypertensive Rats according to blood pressure at random rat be divided into 5 groups: the heart can relax small dose group (3%), middle dosage group (6%), heavy dose of group (12%) and negative control group (normal saline group), positive controls (XINKESHU PIAN group), 10 every group.All animals gastric infusion all then, the administration volume is 1ml/100g, 1/ day, continuous 30 days, respectively at 2 weeks of administration, 3 weeks, 4 all replication rat blood pressures, result of the test saw Table 3-1.
Table 3-1: but heart drop pills is to the influence of renal hypertensive rat blood pressure (x ± SD)
| Group | Dosage (g/kg) | Blood pressure (kpa) before the medicine | 2 weeks day (kpa) behind the medicine | 3 weeks (kpa) behind the medicine | 4 weeks (kpa) behind the medicine |
| The heavy dose of group of dosage group XINKESHU PIAN group in the normal saline group small dose group | -- 5.5 11 22 160 | 29.5±2.1 28.6±1.9 29.6±1.3 28.8±2.3 28.3±1.9 | 30.5±2.5 29.6±2.1 26.4±1.6 ※ 27.6±1.8 ※※ 28.7±1.7 | 29.9±1.9 28.5±1.5 26.9±1.7 ※ 27.3±1.6 ※※ 28.3±1.8 | 30.9±2.3 28.3±1.6 ※ 25.6±1.9 ※※ 26.1±1.6 ※※ 27.8±1.9 ※※ |
Compare ※ p＜0.05, ※ ※ p＜0.01 with the normal saline group; But dosage, heavy dose of group are compared P＜0.05 with positive group in the heart drop pills
Result of the test shows: but heart drop pills can obviously reduce hypertensive rat blood pressure, the reduction amplitude becomes significantly dose-effect relationship with dosage, and strengthens to some extent with the prolongation hypotensive effect of administration time, and antihypertensive effect is better than the XINKESHU PIAN group, has significant difference.
Conclusion: but heart drop pills has significant difference being better than XINKESHU PIAN aspect the reduction hypertensive rat blood pressure.
The specific embodiment:
Further specify the present invention by the following examples.
Embodiment 1:
[prescription]: Radix Puerariae 500g Fructus Crataegi 400g Radix Salviae Miltiorrhizae 400g Radix Notoginseng 20g Radix Aucklandiae 20g
[method for making] above five tastes medical material, Fructus Crataegi, Radix Puerariae, Radix Notoginseng are measured 80% alcohol reflux 2 times for 3 times with each medical material, and 1 hour for the first time, 1 hour for the second time, merge alcohol extract, reclaim ethanol, filtration, filtrate for later use.Radix Salviae Miltiorrhizae extracts three times, adds 95% alcohol reflux 1 hour of 3 times of amounts of medical material for the first time, filters, and filtrate recycling ethanol is to there not being the alcohol flavor; 80% alcohol reflux 1 hour that adds for the second time 3 times of amounts, filter, reclaim ethanol: the water that adds 3 times of amounts of medical material for the third time refluxed 1 hour, filter, merging filtrate is evaporated to the clear paste that relative density is 1.06 (80 ℃ of surveys) jointly with above-mentioned standby filtrate, with 60% alcoholic acid ethyl acetate extraction of equimultiple 3 times, combining extraction liquid, and concentrating under reduced pressure becomes thick paste.Radix Aucklandiae powder is broken into coarse powder, makes solvent according to percolation under fluid extract and the extractum item (" appendix 20 of Chinese pharmacopoeia version in 2000) with 95% ethanol, soaks after 24 hours, and percolation, percolate reclaim the ethanol concentrating under reduced pressure and become thick paste.Above-mentioned thick paste is added in the fused an amount of polyethylene glycol 6000, stir evenly, medicinal liquid is put in the drop pill machine material-storage jar, insulation (80～85 ℃) splashes into 30 droplets/minute droplet speed with water dropper and to be cooled in 5 ℃ of dimethicones, with refrigerative drop pill, absorb coolant, drying is made 10000, promptly.
Embodiment 2:
[prescription]: Radix Puerariae 800g Fructus Crataegi 800g Radix Salviae Miltiorrhizae 800g Radix Notoginseng 60g Radix Aucklandiae 60g
[method for making] above five tastes medical material, Fructus Crataegi, Radix Puerariae, Radix Notoginseng are measured 40% alcohol reflux 2 times for 10 times with each medical material, and 3 hours for the first time, 3 hours for the second time, merge alcohol extract, reclaim ethanol, filtration, filtrate for later use.Radix Salviae Miltiorrhizae extracts three times, adds 60% alcohol reflux 3 hours of 15 times of amounts of medical material for the first time, filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add for the second time 20% alcohol reflux 3 hours of 15 times of amounts, filter, reclaim ethanol; The water that adds 15 times of amounts of medical material for the third time refluxed 3 hours, filter, merging filtrate is evaporated to the clear paste that relative density is 1.12 (80 ℃ of surveys) jointly with above-mentioned standby filtrate, with the ethyl acetate extraction of equimultiple 6 times, combining extraction liquid, and concentrating under reduced pressure becomes thick paste, in 80 ℃ of dryings 8 hours, pulverizes, cross 80 mesh sieves, make dried powder.Radix Aucklandiae powder is broken into coarse powder, makes solvent according to percolation under fluid extract and the extractum item (" appendix 20 of Chinese pharmacopoeia version in 2000) with 60% ethanol, soaks after 24 hours, and percolation, percolate reclaim the ethanol concentrating under reduced pressure and become thick paste.Dried powder is added in the fused an amount of Macrogol 4000, add the thick paste that the Radix Aucklandiae extracts again, stir evenly, medicinal liquid is put in the drop pill machine material-storage jar, insulation (80～85 ℃), splash into and be cooled in 10 ℃ of dimethicones with the speed of dripping of water dropper with 60 droplets/minute, with refrigerative drop pill, absorb coolant, drying, make 10000, promptly.
Embodiment 3:
Radix Puerariae 600g Fructus Crataegi 600g Radix Salviae Miltiorrhizae 600g Radix Notoginseng 40g Radix Aucklandiae 40g
[method for making] above five tastes medical material, Fructus Crataegi, Radix Puerariae, Radix Notoginseng are measured 80% alcohol reflux 2 times for 8 times with each medical material, and 1 hour for the first time, 1 hour for the second time, merge alcohol extract, reclaim ethanol, filtration, filtrate for later use.Radix Salviae Miltiorrhizae extracts three times, adds 95% alcohol reflux 1 hour of 12 times of amounts of medical material for the first time, filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add for the second time 80% alcohol reflux 1 hour of 10 times of amounts, filter, reclaim ethanol; The water that adds 10 times of amounts of medical material for the third time refluxed 1 hour, filter, merging filtrate is evaporated to the clear paste that relative density is 1.08 (80 ℃ of surveys) jointly with above-mentioned standby filtrate, with 30% alcoholic acid ethyl acetate extraction of equimultiple 3 times, combining extraction liquid, and concentrating under reduced pressure becomes thick paste, in 60 ℃ of dryings 8 hours, pulverizes, cross 80 mesh sieves, make dried powder.Radix Aucklandiae powder is broken into coarse powder, makes solvent according to percolation under fluid extract and the extractum item (" appendix 20 of Chinese pharmacopoeia version in 2000) with 90% ethanol, soaks after 24 hours, and percolation, percolate reclaim the ethanol concentrating under reduced pressure and become thick paste.Dried powder is added in the fused an amount of polyethylene glycol 6000, add the thick paste that the Radix Aucklandiae extracts again, stir evenly, medicinal liquid is put in the drop pill machine material-storage jar, insulation (80～85 ℃), splash into and be cooled in 5 ℃ of dimethicones with the speed of dripping of water dropper with 30 droplets/minute, with refrigerative drop pill, absorb coolant, drying, make 10000, promptly.
Embodiment 4:
Radix Puerariae 500g Fructus Crataegi 400g Radix Salviae Miltiorrhizae 400g Radix Notoginseng 20g Radix Aucklandiae 20g
[method for making] above five tastes medical material, Fructus Crataegi, Radix Puerariae, Radix Notoginseng are measured 80% alcohol reflux 2 times for 3 times with each medical material, and 1 hour for the first time, 1 hour for the second time, merge alcohol extract, reclaim ethanol, filtration, filtrate for later use.Radix Salviae Miltiorrhizae extracts three times, adds 95% alcohol reflux 1 hour of 3 times of amounts of medical material for the first time, filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add for the second time 80% alcohol reflux 1 hour of 3 times of amounts, filter, reclaim ethanol; The water that adds 3 times of amounts of medical material for the third time refluxed 1 hour, filtered merging filtrate, be evaporated to the clear paste that relative density is 1.06 (80 ℃ of surveys) jointly with above-mentioned standby filtrate, with 60% alcoholic acid ethyl acetate extraction of equimultiple 3 times, combining extraction liquid, and concentrating under reduced pressure becomes thick paste.Radix Aucklandiae powder is broken into coarse powder, makes solvent according to percolation under fluid extract and the extractum item (" appendix 20 of Chinese pharmacopoeia version in 2000) with 95% ethanol, soaks after 24 hours, and percolation, percolate reclaim the ethanol concentrating under reduced pressure and become thick paste.With the thick paste mixing drying under reduced pressure of dried powder and Radix Aucklandiae extraction, granulate, add starch, the ethanol mixing adds Pulvis Talci, the magnesium stearate tabletting, the bag film-coat is made 1000 tablets of tablets, promptly.
Claims (5)
1, a kind of Chinese medicine extract for the treatment of cardiovascular and cerebrovascular disease, this extract be by Radix Puerariae 500～800g, and Fructus Crataegi 400～800g, Radix Salviae Miltiorrhizae 400～800g, Radix Notoginseng 20～60g, the Radix Aucklandiae 20～60g be through being processed into, and described processing is through following steps:
Step a: Fructus Crataegi, Radix Puerariae, Radix Notoginseng are used ethanol extraction, extracting liquid filtering, filtrate for later use;
Step b: Radix Salviae Miltiorrhizae is with ethanol or water extraction, extracting solution filter filtrate;
The filtrate that step c: step b and step a obtain merges, and concentrates, and with the mixed extractant solvent of ethyl acetate or ethanol and ethyl acetate, extract concentrates, and gets thick paste or dried powder;
Steps d: the Radix Aucklandiae is pulverized and is made solvent with ethanol, soaks, and percolation, percolate reclaims ethanol, is condensed into thick paste,
What step c and steps d obtained is extract of the present invention.
2, the extract of claim 1, in 5 steps of described extract process,
Step a process: Fructus Crataegi, Radix Puerariae, Radix Notoginseng, measure 40～80% alcohol reflux 2 times for 3～10 times with each medical material, 1～3 hour for the first time, 1～3 hour for the second time, merge alcohol extract, reclaim ethanol, filtration, filtrate for later use;
Step b process: Radix Salviae Miltiorrhizae extracts three times, adds 60～95% alcohol refluxs 1～3 hour of 3～15 times of amounts of medical material for the first time, filters, and filtrate recycling ethanol is to there not being the alcohol flavor; Add for the second time 20～80% alcohol refluxs 1～3 hour of 3～15 times of amounts, filter, reclaim ethanol; The water that adds 3～15 times of amounts of medical material for the third time refluxed 1～3 hour, filtered merging filtrate;
Step c process: merge with the standby filtrate of step a, the clear paste that to be evaporated to 80 ℃ of surveys of relative density jointly be 1.06-1.12, with 10～60% alcoholic acid ethyl acetate extractions of the ethyl acetate of equimultiple or equimultiple 3～6 times, combining extraction liquid, and concentrating under reduced pressure becomes thick paste, or with thick paste in 60～80 ℃ of dryings 8 hours, pulverize, cross 80 mesh sieves, get dried powder;
The steps d process: Radix Aucklandiae powder is broken into coarse powder, make solvent according to percolation under Chinese Pharmacopoeia appendix 20 fluid extracts of version in 2000 and the extractum item with 60～95% ethanol, soak after 24 hours, percolation, percolate reclaims the ethanol concentrating under reduced pressure and becomes thick paste, and it is extract of the present invention that step c and steps d obtain.
3, with the Chinese medicine preparation of each extract of claim 1-2 as the active constituents of medicine preparation.
4, the Chinese medicine preparation of claim 3, it is drop pill, it is by in the thick paste or the fused Polyethylene Glycol of dried powder adding that just claim 1 or 2 step c obtain, add the thick paste that right requires 1 or 2 steps d to obtain again, stir evenly, medicinal liquid is put in the drop pill machine material-storage jar, made drop pill with the drop pill machine.
5, the Chinese medicine preparation of claim 4 is characterized in that, described Polyethylene Glycol is the mixture of Macrogol 4000, polyethylene glycol 6000 or Macrogol 4000 and polyethylene glycol 6000.
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| CN103006769A (en) * | 2013-01-05 | 2013-04-03 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof |
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| CN103720810A (en) * | 2012-10-16 | 2014-04-16 | 吉林吉春制药股份有限公司 | Medicine for treating qi-stagnation and blood stasis coronary heart disease and complication of disease and preparation method of medicine |
| CN102988478B (en) * | 2013-01-05 | 2014-11-05 | 山东沃华医药科技股份有限公司 | Traditional Chinese medicine combination for treating cardiovascular and cerebrovascular diseases and preparation method thereof |
| CN105395637A (en) * | 2015-12-23 | 2016-03-16 | 济南陆枋志合信息技术有限公司 | Drug for treating heart disease |
| CN105434583A (en) * | 2015-12-29 | 2016-03-30 | 山东沃华医药科技股份有限公司 | Semi-bionic preparation method for Xinkeshu preparations |
| CN106236874A (en) * | 2016-08-29 | 2016-12-21 | 河北国金药业有限责任公司 | Pharmaceutical composition is as the application in preparation treatment cerebrovascular disease and complication medicine thereof |
| CN108279272B (en) * | 2017-01-06 | 2020-11-27 | 山东沃华医药科技股份有限公司 | Method for simultaneously determining contents of multiple components in Xinkeshu tablet |
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