CN100486615C - Chinese traditional medicine preparation for treating coronary heart disease and angina pectoris and preparation method thereof - Google Patents

Chinese traditional medicine preparation for treating coronary heart disease and angina pectoris and preparation method thereof Download PDF

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CN100486615C
CN100486615C CNB2006102000232A CN200610200023A CN100486615C CN 100486615 C CN100486615 C CN 100486615C CN B2006102000232 A CNB2006102000232 A CN B2006102000232A CN 200610200023 A CN200610200023 A CN 200610200023A CN 100486615 C CN100486615 C CN 100486615C
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叶湘武
王永林
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Guizhou Yibai Pharmaceutical Co Ltd
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Abstract

The invention relates to a traditional Chinese preparation for treating coronary disease and angina pectoris and process for preparation, wherein the preparation comprises (by weight parts) puberulous glochidion herb1-10 parts, haw leaves 1-10 parts, notoginseng 1-10 parts and rhizome of Sichuan lovage 1-10 parts.

Description

Chinese medicine preparation of treatment angina pectoris and preparation method thereof
Technical field: the present invention relates to a kind of Chinese medicine preparation for the treatment of angina pectoris and preparation method thereof, belong to the technical field of herbal pharmaceutical.
Background technology: angina pectoris is meant because coronary atherosclerosis or spasm cause myocardial ischemia, the caused angina pectoris of anoxia, accounts for 90% of patient with angina pectoris.It belongs to one of human major disease, and its mortality rate is first of numerous major diseases always.Angina pectoris is a commonly encountered diseases of internal department, is mainly in middle-older patient, along with the development of society, and the raising of living standards of the people, its age of onset is tending towards rejuvenation.Therefore, the gesture of evidence of coronary heart diseases trend raising, the task of preventing and treating is very heavy, and oneself is through causing domestic and international concern.Along with development of modern science and technology, people have also obtained some progress to coronary heart disease diagnosis and control, as aspect the inspection, by original routine electrocardiogram, load ECG is checked, be updated to ambulatory electrocardiogram, ultrasonic cardiography is checked art, coronary angiography, the application of electron beam ct machine, biochemical analysis and cardiac determination method are also being updated, for early diagnosis provides good means, comprise that aspect preventing and treating the arteria coronaria side props up circulation and set up, the foundation of bypass operation of coronary artery etc., drug treatment, (nitrate on the basis of coronary artery dilating, nitrous acid ester), calcium ion antagonist has appearred, beta-blocker, the application of thrombolytic drug is for the treatment angina pectoris provides multiple means.Yet clinical practice shows that the simple western medicine treatment is only cured the symptoms, not the disease, and especially side effects of pharmaceutical drugs make the patient be difficult to accept and take for a long time.The hope that the contemporary mankind goes back to nature is strong day by day, generally wishes the treatment by Chinese herbs of natural nuisance-free, thereby provides excellent opportunity for the development of Chinese medicine.Angina pectoris is referred to as obstruction of qi in the chest and cardialgia in the traditional Chinese medical science, the pure Chinese medicinal preparation of developing a kind of efficient, low toxicity, steady quality, dosage form advanced person's treatment angina pectoris is a purpose of the present invention.The angina pectoris state of an illness breaks with tremendous force, and patient's body and mind is caused great injury, therefore, usually needs a kind of relief of symptoms rapidly, releasing patient misery, rapid, the outstanding effect medicine of onset clinically.
Summary of the invention:
The objective of the invention is to: a kind of Chinese medicine preparation for the treatment of angina pectoris and preparation method thereof is provided, and said preparation is based on soft capsule and drop pill; The present invention is on the basis of folk remedy, clinical practice, prescription and herb resource to we are investigated, on a large amount of pharmacy and pharmacological testing research basis, utilize modern technologies that the quality of preparation Chinese crude drug, pharmacology, toxicology, Natural Medicine Chemistry, preparation process, quality standard etc. are studied, having prescription simplifies, the dosage form novelty, clinical practice is safe and effective, quality controllable, disintegrate is fast, absorbs, produce effects is fast, dose is little, the bioavailability height, determined curative effect, advantages such as good stability.
The present invention constitutes like this: calculate according to composition by weight: it is prepared from acceptable dosage form on drop pill, tablet, the watered pill, capsule, granule, electuary, liquid preparation, powder agent, pill, soft capsule, suspending agent, spray, aerosol, injectable powder and other pharmaceutics for 1~10 part by 1~10 part of Herba Polygoni Orientalis, 1~10 part of Folium Crataegi, 1~10 part of Radix Notoginseng and Rhizoma Chuanxiong.Specifically, calculate according to composition by weight: it is prepared from soft capsule or drop pill for 3 parts by 5 parts of Herba Polygoni Orientaliss, 4 parts of Folium Crataegi, 3 parts of Radix Notoginseng and Rhizoma Chuanxiong.
The preparation method of the Chinese medicine preparation of treatment angina pectoris is: Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng decoct with water, and filtrate concentrates, precipitate with ethanol, leave standstill, filtrate recycling ethanol also concentrates thin up, last macroporous adsorptive resins washes with water earlier, discards water lotion, continue with 20~95% ethanol elutions, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; The Rhizoma Chuanxiong pulverizing medicinal materials is used supercritical carbon dioxide extraction, collects extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
Concrete method is: Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 5~20 times of water gagings and decoct 1~5 time, each 0.5~3 hour, filter, merging filtrate, be evaporated to relative density 1.02~1.20, add ethanol and make and contain alcohol amount and reach 20~90%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.05~1.20, adds the suitable quantity of water dilution, the macroporous adsorptive resins of last blade diameter length ratio 1: 2~25, absorption flow velocity 0.5~5BVh -1, discard and penetrate liquid, with 0.5~10BV washing, flow velocity 0.5~5BVh -1, discard water lotion, continue with 0.5~10BV20~95% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 0.5~5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve 1~No. 5, uses supercritical carbon dioxide extraction, with pressure is that 5~80MP, temperature are that 15~80 ℃, flow are condition extraction 0.5~10h of 5~100L/h, resolve pressure 5~30MP, 15~80 ℃ of temperature are collected extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
This Chinese medicine preparation can also prepare like this: Herba Polygoni Orientalis, Folium Crataegi decoct with water, and filter merging filtrate, concentrating under reduced pressure, precipitate with ethanol leaves standstill, filtrate recycling ethanol also concentrates thin up, last macroporous adsorptive resins, wash with water earlier, discard water lotion, continue with 20~95% ethanol elutions, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Radix Notoginseng decocts with water, and filters merging filtrate, concentrating under reduced pressure, precipitate with ethanol leaves standstill, sucking filtration, decompression filtrate recycling ethanol also concentrates thin up, last macroporous adsorptive resins, wash with water earlier, discard water lotion, continue with 20~95% ethanol elutions, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; The Rhizoma Chuanxiong pulverizing medicinal materials is used supercritical carbon dioxide extraction, collects extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
Concrete method is: Herba Polygoni Orientalis, Folium Crataegi add 5~20 times of water gagings and decoct 1~5 time, each 0.5~3 hour, filter, merging filtrate, be evaporated to relative density 1.05~1.20, add ethanol and make and contain alcohol amount and reach 20~90%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.05~1.20, adds the suitable quantity of water dilution, the macroporous adsorptive resins of last blade diameter length ratio 1: 2~25, absorption flow velocity 0.5~5BVh -1, discard and penetrate liquid, with 0.5~10BV washing, flow velocity 0.5~5BVh -1, discard water lotion, continue with 0.5~10BV20~95% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 0.5~5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Radix Notoginseng adds 5~20 times of water gagings and decocts 1~5 time, each 0.5~5 hour, filters, merging filtrate is evaporated to 50 ℃ of relative densities 1.02~1.20, adds ethanol and makes and contain alcohol amount and reach 20~90%, stir, left standstill sucking filtration, decompression filtrate recycling ethanol 12 hours, and be concentrated into relative density 1.05~1.20, add the suitable quantity of water dilution, the macroporous adsorptive resins of last blade diameter length ratio 1: 2~25, absorption flow velocity 0.5~5BVh -1, discard and penetrate liquid, with 0.5~10BV washing, flow velocity 0.5~5BVh -1, discard water lotion, continue with 0.5~10BV20~95% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 0.5~5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve 1~No. 5, uses supercritical carbon dioxide extraction, with pressure is that 5~80MP, temperature are that 15~80 ℃, flow are condition extraction 0.5~10h of 5~100L/h, resolve pressure 5~30MP, 15~80 ℃ of temperature are collected extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
Soft capsule in the described preparation prepares like this: extract obtained adding contains 0.1~30% mellisic vegetable oil, mix homogeneously in right amount; With gelatin: glycerol: distilled water: antiseptic=0.8~1.1: 0.2~0.6: 0.6~1.1: 0.001~0.005 preparation capsule material, compacting promptly.
Drop pill in the described preparation prepares like this: behind the extract obtained mix homogeneously, in medicated powder: the ratio of substrate=1: 1~3 feeds intake, earlier with after the substrate fusion, add the medicated powder mixing,, splash in the middle of the condensed fluid with 20~60 droplets/minute speed 70~80 ℃ of insulations down, the condensation molding, collect drop pill, absorb condensed fluid with filter paper, promptly.
Used macroporous adsorptive resins model can be D 101, AB-8, DA 201, D 3520, D 4006, D 4020, DB 301Or X-5.
Described drying can adopt microwave vacuum drying, reduced vacuum drying, spray drying or lyophilization.
Used vegetable oil can be a kind of or several miscella of soybean oil, Oleum Arachidis hypogaeae semen, Oleum Camelliae, and also available arene, organic acid, glycerol, isopropyl alcohol or surfactant replace.
Used antiseptic is that mud pool tortoise beetle ester, mud moor gold ethyl ester, mud are moored one or several the mixture in the golden propyl ester.
Used substrate can be one or more the mixture in Polyethylene Glycol-6000 or Polyethylene Glycol-400, polyoxyethylene monostearate, sodium stearate, poloxamer, stearic acid, glyceryl monostearate, the insect wax.
Used condensed fluid can be dimethicone, liquid Paraffin, vegetable oil or their mixture.
Function of the present invention cures mainly: have blood circulation promoting and blood stasis dispelling, coronary circulation-promoting pain-relieving function.Be used for the angina pectoris heart blood silt, disease is seen uncomfortable in chest, stabbing pain over the chest does not fixingly move, palpitation and uneasiness, and words are dark violet, and angina pectoris such as thready and hesitant pulse are seen above-mentioned patient.
Side of the present invention separates: the generation according to " obstruction of qi in the chest and cardialgia " must have internal organs deficient earlier, imbalance of YIN and YANG, heresies such as the expectorant that continues then is turbid, blood stasis, cold and heat are taken advantage of it, and cause the etiology and pathogenesis that primary disease is brought out in the resistance of the heart arteries and veins stasis of blood, abide by " pain is then obstructed; logical and not bitterly " reason, take blood circulation promoting and blood stasis dispelling, the method for coronary circulation-promoting pain-relieving, fully take into account simultaneously the Dialectic Relationship of QI and blood again, make gas help blood capable, the capable then stasis of blood of blood scattered pulse is logical, and beniol then pain promptly ends.The side is with the Herba Polygoni Orientalis acrid in the mouth, and is cool in nature, invigorates blood circulation, dissipating blood stasis, pain relieving be monarch drug; Be aided with Radix Notoginseng, Folium Crataegi is declared smooth heart-yang, mediation heart arteries and veins is removed stasis of blood resistance, eliminating stasis to stop pain; The then hot temperature of loosing of Rhizoma Chuanxiong is logical, is the gas medicine in the blood, and the merit of sensible QI and blood is arranged, and helps QI-blood circulation, and what use is that assistant makes.Full side is with hot, Gan Weizhu, and is warm, cool parallel.Hot can dissipating blood stasisization stagnating, temperature can pass through blood vessels, promote that blood is capable; Sweet slow temperature is logical, and hardship is fallen and let out, dissipating blood stasis and blood, the stasis of blood loose then blood from return through.All medicines mutually and, play blood circulation promoting and blood stasis dispelling altogether, the merit of coronary circulation-promoting pain-relieving suits pathogenesis.Quan Fangxin looses warm logical, and sweet benefit hardship is rushed down, dissipating blood stasis and blood, and at the excess pathogen side of the sending medication of " obstruction of qi in the chest and cardialgia ", useful YAOJING letter power is special, does not have the cooler fraud of temperature partially, meets traditional Chinese medical science prescription theory, and effect is remarkable.
Range of application of the present invention: this medicament is used for the angina pectoris heart blood silt, and disease is seen uncomfortable in chest, stabbing pain over the chest does not fixingly move, palpitation and uneasiness, and words are dark violet, and angina pectoris such as thready and hesitant pulse are seen above-mentioned patient.
Compared with prior art, preparation of the present invention has the effect of blood circulation promoting and blood stasis dispelling, coronary circulation-promoting pain-relieving, can alleviate anginal symptoms such as stagnation of heart-blood rapidly, and onset is rapid, and effect is obvious; Its prescription is simplified, the dosage form novelty, and clinical practice is safe and effective, and is quality controllable; And it is fast to have a disintegrate, absorbs, produce effects is fast, and dose is little, bioavailability height, determined curative effect, advantages such as good stability.
The applicant has carried out series of experiment research, to screen preparation technology of the present invention and to prove its effect.
One, the selection of technology of the present invention
For the Herba Polygoni Orientalis in this preparation process, Folium Crataegi extract except that macroporous adsorbent resin purifies, still can adopt the separation and purification of organic solvent extraction mode, concrete grammar is with water extract-alcohol precipitation liquid decompression recycling ethanol and is concentrated into relative density 1.05~1.20, measure n-butanol extraction 1~10 time with 0.2~5 times, merging the back washes 1~10 time with 0.2~2 times of water gaging, discard water lotion, reclaim n-butyl alcohol, be condensed into thick paste, residue carries out microwave vacuum drying (or reduced vacuum, spraying, lyophilization), be ground into fine powder, get extract.But adopt this technology that following drawback is arranged: to introduce a large amount of organic solvents, bring very big inconvenience for product post processing and quality control; The organic solvent extraction mode is difficult under real working condition to realize that equipment is had certain requirement, promptly allows to produce, and cost is also higher relatively; In addition, a large amount of Recovery of Organic Solvent or discharging also can increase production cost, are unfavorable for environmental protection.And the applicant has confirmed no matter to use macroporous adsorbent resin or organic solvent extraction mode by experiment, and the transfer of index components in the middle of the medical material be there is no too big influence.So the present invention adopts macroporous adsorbent resin to make with extra care purification.
2. the Rhizoma Chuanxiong medical material contains the volatile ingredient that has pharmacologically active in a large number, tackles it and extracts.Traditional method is a steam distillation, and Modern New Technology adopts Co 2 supercritical fluid (CO 2-SFE) the pharmacological component in the extraction Rhizoma Chuanxiong medical material.For whether using entrainer technical conditions such as (can be methanol, ethanol or acetone) in the middle of the extraction scheme of volatile ingredient and the supercritical fluid extraction volatile ingredient process, the applicant has carried out the experiment contrast from the material base and the pharmacodynamics effect of extract, found that no matter supercritical fluid extraction still all is being better than traditional steam distillation to the extracted amount of index components aspect the pharmacodynamics effect intensity, and use entrainer whether the extracted amount and the pharmacodynamics effect of index components not to be had the significance influence.Therefore, co_2 supercritical fluid extraction is adopted in the extraction of Rhizoma Chuanxiong medical material among the present invention, does not use entrainer.
3. the present invention's employed substrate in preparations shaping can be one or more miscella or arene, organic acid, glycerol, isopropyl alcohol and the surfactant in oleaginous base such as soybean oil, Oleum Arachidis hypogaeae semen, the Oleum Camelliae; Non-oleaginous base such as PEG400~6000 (PEG400~6000); Antiseptic can be that mud pool tortoise beetle ester, mud moor gold ethyl ester, mud are moored one or more the mixing in the golden propyl ester.But find by test, if adopt the PEG class following drawback to be arranged as substrate: since PEG have certain draw moist, when PEG is made into medicinal liquid when being filled in capsule shells as substrate, absorb the moisture in the glue shell easily and moisture is moved into the CF body from softgel shell, this transfer is very fast, gross weight can reach CF heavy 20%.When being the substrate preparating liquid with PEG, because medicine is water miscible, the active component of medicine can be moved to the softgel shell outer wall.With PEG is the soft capsule of disperse medium (substrate) preparation, its dry run is different with the soft capsule that with the vegetable oil is disperse medium (substrate) preparation, the former is difficult for grasping drying time, time is oversize, can make softgel shell embrittlement, time is too short, because the liquid aqueous finished product seepage in storage period that causes in the soft capsule.In addition, with PEG be the medicinal liquid compacting soft capsule of substrate preparation after because the hydrophilic of PEG can cause the softgel shell hardening with moisture absorption in the glue shell.Therefore, the present invention selects oleaginous base (one or more in soybean oil, Oleum Arachidis hypogaeae semen, the Oleum Camelliae) or arene, organic acid, glycerol, isopropyl alcohol and surfactant for use.
Two, pharmacodynamic study
The factor that influences curative effect of medication is a lot, as the technology and the dosage form of the chemical property of medicine and physical property, preparation.Thicker relatively as hard capsule, tablet etc. for adapting to commercial production needs drug prepared granule, oral entering needs behind the human body by the dissolving absorption process, granularity is very big to the influence of medicine biological effectiveness, and the medicine of this soft capsule is fine and smooth and even, improved the specific surface area of medicine by the change of this physical property, made its enhanced dissolution rate in gastrointestinal tract, infiltration rate is also accelerated, utilization to the medicine active substance also improves, thereby curative effect also significantly improves; Simultaneously in other dosage forms as molding such as hard capsule, tablets on normal interpolation solid adjuvant material, these all influence the dissolving and the absorption of preparation easily, in addition, hard capsule, tablet, granule are solid preparation, general in the mill just even relatively, so curative effect is not necessarily stable, and this soft capsule mostly is semisolid, mixing uniformity is good, thereby has guaranteed the stable homogeneous of pharmaceutical effectiveness effectively.For proving science of the present invention, effectiveness, the applicant has carried out experimentation:
1. ligation rat arteria coronaria left anterior descending branch is caused the influence of acute myocardial infarction
Get 60 of SD rats, be divided into 6 groups at random: sham operated rats (normal saline 10ml/kg), model group (normal saline 10ml/kg), compound Salviae Miltiorrhizae group (2.0g crude drug/kg), high dose group (8.0g crude drug/kg), middle dosage group (4.0g crude drug/kg), low dosage (the 2.0g crude drug/kg), every group 10, male and female half and half.Every day, gastric infusion was 1 time, successive administration 3 days, half an hour after the administration in the 3rd day, experimental rat 20% urethane lumbar injection 1.0g/kg anesthesia is fixed on the Mus plate, the record normal ECG, breast the 4th, 5 ribs are cut off skin on a rat left side, separate chest muscle, expose the 4th, 5 ribs, enclose otch and do a pocket sealing.Rat is connect respirator oxygen supply mask oxygen inhalation, separate the 4th, 5 ribs and use the drag hook permanent opening with mosquito forceps, clamp happy peplos, extrude heart, between arterial cone and left auricle, find arteria coronaria left anterior descending branch accompanying vein, connect bundle rapidly and send heart back to thoracic cavity, extrude the air in thoracic cavity, the knotting of tension pocket sealing.Recover to breathe, recording ecg has the obvious J person of raising to be the successful sign of operation (reject and obvious myocardial infarction electrocardiographic wave person do not occur).Before the record ligation, after the ligation 15,30,60,90,120,180min two lead electrocardiogram, the back 180 minutes femoral artery of performing the operation are got blood, centrifuging and taking serum ,-20 degree are preserved, and are equipped with thought-read creatase LDH, CK.It is dirty with the residual blood of normal saline flush away to core, take by weighing ventricular weight, freezing 0.5 hour of refrigerator, taking-up is cut into 5,37 ℃ were dyeed 10 minutes in 1% TTC liquid, took out with normal saline flush away residual liquid, cut infarcted region (being canescence) and weighed, be calculated as follows myocardial ischemia district percentage rate, carry out statistical disposition.
To the infarction fraction values influence of myocardial infarction due to the rat coronary ligation (X ± S), n=10
Group Dosage g crude drug/kg Heavy (g) whole-heartedly Ventricle heavy (g) Infarcted myocardium heavy (g) Infarcted region/(%) whole-heartedly Infarcted region/ventricle (%)
Sham operated rats 0.83 ±0.15 0.78 ±0.14 0.00 ±0.00 0.00 ±0.00 0.00 ±0.00
Model group 0.88 ±0.17 0.83 ±0.15 0.20 ±0.05 22.88 ±4.84 24.08 ±5.03
FUFANG DANSHEN PIAN 2.0 0.90 ±0.13 0.84 ±0.12 0.14 ±0.05 15.96** ±5.45 17.08** ±5.82
High dose group 8.0 0.87 ±0.16 0.81 ±0.16 0.11 ±0.02 12.98** ±1.88 14.02** ±1.88
Middle dosage group 4.0 0.84 ±0.15 0.80 ±0.14 0.15 ±0.02 17.81* ±3.00 19.16* ±3.27
Low dose group 2.0 0.84 ±0.20 0.80 ±0.19 0.14 ±0.04 17.56* ±5.17 18.49* ±5.49
To the J point value of raising influence of myocardial infarction due to the rat coronary ligation (X ± S), n=10
Figure C200610200023D00101
Figure C200610200023D00111
To LDH, the CK influence of myocardial infarction due to the rat coronary ligation (X ± S)
Dosage g crude drug/kg LDH(U/L) CK(U/L)
Sham operated rats 3047.95±823.98 197.39±69.35
Model group 6205.48±853.77# 292.70±59.63#
The compound Salviae Miltiorrhizae group 2.0 4917.81±1639.33* 241.22±62.09
High dose group 8.0 4048.71±1460.79** 216.04±40.30**
Middle dosage group 4.0 4294.52±1381.25** 228.37±61.27*
Low dose group 2.0 5229.45±877.44* 236.00±44.42*
Compare with sham operated rats: #p<0.05, ##p<0.01;
Each dosage group and model group compare: * p<0.05, * * p<0.01.
Result of the test shows: each dosage group can reduce the infarction rate of myocardial infarction due to the rat coronary ligation, makes the reduction of raising of infarction electrocardiogram J point, reduces LDH in the serum, and the vigor of CK, with model group comparing difference significantly (P<0.05, P<0.01).Show that preparation of the present invention improves significantly to the myocardial ischemia tool due to the rat coronary ligation, can obviously alleviate degree of myocardial ischemia.
2. to myocardial infarction influence due to the anesthetized dog coronary ligation
30 of hybrid dogs, body weight are 7.5~13.0Kg, and the male and female dual-purpose is divided into 6 groups at random, i.e. (1) sham operated rats: give the isometric(al) normal saline.(2) model group: give the isometric(al) normal saline.(3) FUFANG DANSHEN PIAN group: FUFANG DANSHEN PIAN 1.0g.kg -1(4) high dose group: 3.0g.kg -1(5) dosage group: 1.5g.kg in -1(6) low dose group: 0.75g.kg -1Each organizes the administration volume is 2ml/kg.Every group of 5 animals.After anaesthetizing with 3% pentobarbital sodium 1ml/kg by the latent venule of forelimb, be fixed on the operating-table, cut off the hair of cervical region, chest and left hind inboard.It is subcutaneous that needle electrode is inserted extremity, recording ecg (ECG).Fourth, fifth intercostal is opened breast in the left side, exposes heart, and connects artificial respirator.Femoral venous catheter waits in order to intravenous drip and oozes G/NS.Open pericardium, be sewn in thoracic wall, make the pocket cradle.With descending 1/3 place, the not ligation of threading of pseudo-operation group in No. 0 silk thread ligation ramus descendens anterior arteriae coronariae sinistrae.Open abdomen in the prominent left side down of arrow and find duodenum, 30min is the 5ml/kg administration by the administration volume before the ligation.12 the mapping point seams in position are put the epicardial electrogram electrode near selecting infarct, and selecting a control point away from infarct, carry out mapping with hand-held insulated metal point-like electrode by the mapping dot sequency, (the calibration: 1mv=5mm) of electrocardiograph record epicardial electrogram (EECG).Add up ST field offset Σ-ST and the N-ST of each mapping point EECG.Before the ligation, got femoral vein in 60 minutes, 120 minutes after the ligation and get blood, centrifuging and taking serum is with kit measurement serum CK, LDH value.After experiment finishes, take out heart immediately, behind normal saline flush away blood, take by weighing heavy whole-heartedly and ventricular weight, and the ventricle crosscut become 5, and place 37 ℃ of 1%TTC solution 15min that dyes, cut off the non-infarct that each myocardium sheet is colored, undyed infarct cardiac muscle is weighed, obtain infarction size heavily respectively divided by heavy or ventricle whole-heartedly and account for heavy whole-heartedly or account for the heavy percentage ratio of ventricle.
Influence (X ± S mv) to myocardial infarction Σ-ST due to the anesthetized dog coronary ligation
Group Dosage g crude drug/kg Before the ligation After the ligation 30 After the ligation 60 After the ligation 120 After the ligation 180
Sham operated rats 14.28±5.56 17.00±8.13 18.40±8.63 14.85±6.08 15.12±8.27
Model group 14.28±7.19 64.47±8.82 58.24±14.04 56.20±14.50 60.00±8.35
Compound Salviae Miltiorrhizae 1.0 25.04±9.51 53.92± 19.69* 49.12± 15.19* 44.16± 16.22* 38.36± 14.53*
High dose group 3.0 20.56±6.50 45.28± 10.02* 40.92± 13.97** 33.08± 8.44** 33.40± 9.10**
Middle dosage group 1.5 22.52±4.96 43.16± 13.06* 40.76± 12.04* 35.02±9.42* 29.96± 19.56**
Low dose group 0.75 31.36±9.62 60.00±27.59 52.46± 16.12* 45.52± 14.66* 46.44± 18.47*
To the serum CK of myocardial infarction due to the anesthetized dog coronary ligation, LDH influence (X ± S)
Figure C200610200023D00131
To the influence of anaesthetizing myocardial infarct size due to the big coronary ligation (X ± S)
Group Dosage g crude drug/kg Heavy (g) whole-heartedly Ventricle heavy (g) Infarcted myocardium heavy (g) Infarcted region/(%) whole-heartedly Infarcted region/ventricle (%)
Sham operated rats 72.64 ±6.77 64.78 ±5.38 0.00 ±0.00 0.00 ±0.00 0.00 ±0.00
Model group 59.80 ±16.21 51.46 ±13.25 7.62 ±1.85 12.74 ±2.64 14.81 ±1.60
FUFANG DANSHEN PIAN 1.0 76.60 ±5.59 68.36 ±4.82 7.78 ±1.54 10.16 ±1.79** 11.37 ±1.97*
High dose group 3.0 65.04 ±9.50 58.22 ±7.95 5.48 ±2.27 8.43 ±2.51* 9.25 ±2.80**
Middle dosage group 1.5 87.30 ±13.53 78.10 ±11.15 8.24 ±3.64 9.38 ±1.61** 10.56 ±1.59**
Low dose group 0.75 76.56 ±16.14 68.50 ±14.96 7.34 ±3.06 9.59 ±3.40** 10.81 ±3.80**
N=5, each dosage group is compared with model group: * p<0.05, * * p<0.01.
Result of the test shows: all can obviously alleviate (the Σ-ST) of degree of myocardial ischemia due to the anesthetized dog coronary ligation after each dosage group administration, reduce LDH in the serum, and the vigor of CK, myocardial infarct size due to the minimizing anesthetized dog coronary ligation, with model group comparing difference remarkable (p<0.05,0.01), show that preparation of the present invention improves significantly to the myocardial ischemia tool of anesthetized dog anterior descending coronary caused by ligature, can obviously alleviate degree of myocardial ischemia.
The specific embodiment:
Embodiments of the invention 1: 5 parts of Herba Polygoni Orientaliss, 4 parts of Folium Crataegi, 3 parts of Radix Notoginseng and 3 parts of Rhizoma Chuanxiongs (part is a weight portion, and following examples are weight portion)
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 10 times of water gagings and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to relative density 1.10, add ethanol and make and contain alcohol amount and reach 65%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.07, adds the suitable quantity of water dilution, 1: 10 D of last blade diameter length ratio 101Macroporous adsorptive resins, absorption flow velocity 2BVh -1, discard and penetrate liquid, with 1BV washing, flow velocity 2BVh -1, discard water lotion, continuing and using 3BV70% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 2BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out microwave vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 3, use supercritical carbon dioxide extraction, is that 30MP, temperature are that 50 ℃, flow are the condition extraction 4h of 20L/h with pressure, resolves pressure 10MP, 40 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and add again and contain 2% mellisic soybean oil in right amount, mix homogeneously, standby; With gelatin: glycerol: distilled water: antiseptic (mud pool tortoise beetle ester)=1: 0.4: 1: 0.002 preparation capsule material, compacting promptly getting soft capsule; This product oral, 3 times on the one, each 2.
Embodiments of the invention 2: 1 part of 1 part of Herba Polygoni Orientalis, 1 part of Folium Crataegi, 1 part of Radix Notoginseng and Rhizoma Chuanxiong
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 5 times of water gagings and decoct 1 time, each 0.5 hour, filter, merging filtrate, be evaporated to relative density 1.02, add ethanol and make and contain alcohol amount and reach 20%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.05, adds the suitable quantity of water dilution, 1: 2 AB-8 macroporous adsorptive resins of last blade diameter length ratio, absorption flow velocity 0.5BVh -1, discard and penetrate liquid, with 0.5BV washing, flow velocity 0.5BVh -1, discard water lotion, continuing and using 0.5BV20% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 0.5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out the reduced vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 1, use supercritical carbon dioxide extraction, is that 5MP, temperature are that 15 ℃, flow are the condition extraction 0.5h of 5L/h with pressure, resolves pressure 5MP, 15 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and add again and contain 0.1% mellisic Oleum Arachidis hypogaeae semen in right amount, mix homogeneously, standby; With gelatin: glycerol: distilled water: antiseptic (mud moor gold ethyl ester)=0.8: 0.6: 0.6: 0.005 preparation capsule material, compacting promptly getting soft capsule.
Embodiments of the invention 3: 10 parts of 10 parts of Herba Polygoni Orientaliss, 10 parts of Folium Crataegi, 10 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 20 times of water gagings and decoct 5 times, each 3 hours, filter merging filtrate, be evaporated to relative density 1.20, add ethanol and make and contain alcohol amount and reach 90%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.20, adds the suitable quantity of water dilution, 1: 25 DA of last blade diameter length ratio 201Macroporous adsorptive resins, absorption flow velocity 5BVh -1, discard and penetrate liquid, with 10BV washing, flow velocity 5BVh -1, discard water lotion, continuing and using 10BV95% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 5, use supercritical carbon dioxide extraction, is that 80MP, temperature are that 80 ℃, flow are the condition extraction 10h of 100L/h with pressure, resolves pressure 30MP, 80 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and add again and contain 30% mellisic Oleum Camelliae in right amount, mix homogeneously, standby; With gelatin: glycerol: distilled water: antiseptic (mud is moored golden propyl ester)=1.1: 0.2: 1.1: 0.001 preparation capsule material, compacting promptly getting soft capsule.
Embodiments of the invention 4: 6 parts of 9 parts of Herba Polygoni Orientaliss, 8 parts of Folium Crataegi, 6 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 15 times of water gagings and decoct 4 times, each 2 hours, filter merging filtrate, be evaporated to relative density 1.15, add ethanol and make and contain alcohol amount and reach 75%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.15, adds the suitable quantity of water dilution, 1: 20 D of last blade diameter length ratio 3520Macroporous adsorptive resins, absorption flow velocity 3BVh -1, discard and penetrate liquid, with 5BV washing, flow velocity 3BVh -1, discard water lotion, continuing and using 5BV60% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 3BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out lyophilization, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 4, use supercritical carbon dioxide extraction, is that 60MP, temperature are that 60 ℃, flow are the condition extraction 6h of 70L/h with pressure, resolves pressure 20MP, 60 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, mix homogeneously, in medicated powder: the ratio of substrate (Polyethylene Glycol-6000 and Polyethylene Glycol-400)=1: 2 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 75 ℃ of insulations down, splash in the middle of the condensed fluid (dimethicone) with 40 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly get drop pill.
Embodiments of the invention 5: 4 parts of 7 parts of Herba Polygoni Orientaliss, 6 parts of Folium Crataegi, 4 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 12 times of water gagings and decoct 2 times, each 1.5 hours, filter merging filtrate, be evaporated to relative density 1.08, add ethanol and make and contain alcohol amount and reach 55%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.10, adds the suitable quantity of water dilution, 1: 15 D of last blade diameter length ratio 4006Macroporous adsorptive resins, absorption flow velocity 1BVh -1, discard and penetrate liquid, with 2BV washing, flow velocity 1BVh -1, discard water lotion, continuing and using 2BV40% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 1BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out microwave vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 2, use supercritical carbon dioxide extraction, is that 15MP, temperature are that 30 ℃, flow are the condition extraction 2h of 50L/h with pressure, resolves pressure 15MP, 25 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, mix homogeneously, in medicated powder: the ratio of substrate (polyoxyethylene monostearate)=1: 1 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 70 ℃ of insulations down, splash in the middle of the condensed fluid (liquid Paraffin) with 20 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly get drop pill.
Embodiments of the invention 6: 10 parts of 1 part of Herba Polygoni Orientalis, 10 parts of Folium Crataegi, 10 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 8 times of water gagings and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to relative density 1.05, add ethanol and make and contain alcohol amount and reach 40%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.12, adds the suitable quantity of water dilution, 1: 5 D of last blade diameter length ratio 4020Macroporous adsorptive resins, absorption flow velocity 4BVh -1, discard and penetrate liquid, with 8BV washing, flow velocity 4BVh -1, discard water lotion, continuing and using 8BV80% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 4BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out the reduced vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 3, use supercritical carbon dioxide extraction, is that 50MP, temperature are that 40 ℃, flow are the condition extraction 8h of 90L/h with pressure, resolves pressure 25MP, 50 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, mix homogeneously, in medicated powder: the ratio of substrate (sodium stearate and stearic acid)=1: 3 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 80 ℃ of insulations down, splash in the middle of the condensed fluid (vegetable oil) with 60 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly get drop pill.
Embodiments of the invention 7: 2 parts of 2 parts of Herba Polygoni Orientaliss, 2 parts of Folium Crataegi, 3 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi add 10 times of water gagings and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to relative density 1.10, add ethanol and make and contain alcohol amount and reach 65%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.07, adds the suitable quantity of water dilution, 1: 10 DB of last blade diameter length ratio 301Macroporous adsorptive resins, absorption flow velocity 2BVh -1, discard and penetrate liquid, with 1BV washing, flow velocity 2BVh -1, discard water lotion, continuing and using 3BV70% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 2BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Radix Notoginseng adds 10 times of water gagings and decocts 3 times, each 2 hours, filters, merging filtrate, be evaporated to 50 ℃ of relative densities 1.10, add ethanol and make and contain alcohol amount and reach 65%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol, and be concentrated into relative density 1.07, add the suitable quantity of water dilution, 1: 10 DB of last blade diameter length ratio 301Macroporous adsorptive resins, absorption flow velocity 2BVh -1, discard and penetrate liquid, with 1BV washing, flow velocity 2BVh -1, discard water lotion, continuing and using 3BV70% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 2BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 3, use supercritical carbon dioxide extraction, is that 30MP, temperature are that 50 ℃, flow are the condition extraction 4h of 20L/h with pressure, resolves pressure 10MP, 40 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and add again and contain 2% mellisic soybean oil and Oleum Camelliae in right amount, mix homogeneously, standby; With gelatin: glycerol: distilled water: antiseptic (mud pool tortoise beetle ester and mud moor gold ethyl ester)=1: 0.4: 1: 0.002 preparation capsule material, compacting promptly getting soft capsule.
Embodiments of the invention 8: 1 part of 3 parts of Herba Polygoni Orientaliss, 1 part of Folium Crataegi, 2 parts of Radix Notoginseng and Rhizoma Chuanxiong
Herba Polygoni Orientalis, Folium Crataegi add 5 times of water gagings and decoct 1 time, each 2.5 hours, filter, merging filtrate, be evaporated to relative density 1.05, add ethanol and make and contain alcohol amount and reach 20%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.05, adds the suitable quantity of water dilution, 1: 2 X-5 macroporous adsorptive resins of last blade diameter length ratio, absorption flow velocity 0.5BVh -1, discard and penetrate liquid, with 0.5BV washing, flow velocity 0.5BVh -1, discard water lotion, continuing and using 0.5BV20% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 0.5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out lyophilization, is ground into fine powder, gets extract; Radix Notoginseng adds 5 times of water gagings and decocts 1 time, each 0.5 hour, filters, merging filtrate is evaporated to 50 ℃ of relative densities 1.02, adds ethanol and makes and contain alcohol amount and reach 20%, stir, left standstill sucking filtration, decompression filtrate recycling ethanol 12 hours, and be concentrated into relative density 1.05, add the suitable quantity of water dilution, 1: 2 X-5 macroporous adsorptive resins of last blade diameter length ratio, absorption flow velocity 0.5BVh -1, discard and penetrate liquid, with 0.5BV washing, flow velocity 0.5BVh -1, discard water lotion, continuing and using 0.5BV20% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 0.5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out lyophilization, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 1, use supercritical carbon dioxide extraction, is that 5MP, temperature are that 15 ℃, flow are the condition extraction 0.5h of 5L/h with pressure, resolves pressure 5MP, 15 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and add again and contain 0.1% mellisic soybean oil and Oleum Arachidis hypogaeae semen in right amount, mix homogeneously, standby; With gelatin: glycerol: distilled water: antiseptic (mud moor gold ethyl ester and mud are moored golden propyl ester)=0.8: 0.6: 0.6: 0.005 preparation capsule material, compacting promptly getting soft capsule.
Embodiments of the invention 9: 2 parts of 4 parts of Herba Polygoni Orientaliss, 3 parts of Folium Crataegi, 1 part of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi add 20 times of water gagings and decoct 5 times, each 3 hours, filter merging filtrate, be evaporated to relative density 1.20, add ethanol and make and contain alcohol amount and reach 90%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.20, adds the suitable quantity of water dilution, 1: 25 D of last blade diameter length ratio 101Macroporous adsorptive resins, absorption flow velocity 5BVh -1, discard and penetrate liquid, with 10BV washing, flow velocity 5BVh -1, discard water lotion, continuing and using 10BV95% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out microwave vacuum drying, is ground into fine powder, gets extract; Radix Notoginseng adds 20 times of water gagings and decocts 5 times, each 5 hours, filters, merging filtrate, be evaporated to 50 ℃ of relative densities 1.20, add ethanol and make and contain alcohol amount and reach 90%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol, and be concentrated into relative density 1.20, add the suitable quantity of water dilution, 1: 25 D of last blade diameter length ratio 101Macroporous adsorptive resins, absorption flow velocity 5BVh -1, discard and penetrate liquid, with 10BV washing, flow velocity 5BVh -1, discard water lotion, continuing and using 10BV95% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out microwave vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 5, use supercritical carbon dioxide extraction, is that 80MP, temperature are that 80 ℃, flow are the condition extraction 10h of 100L/h with pressure, resolves pressure 30MP, 80 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and add again and contain 30% mellisic Oleum Arachidis hypogaeae semen and Oleum Camelliae in right amount, mix homogeneously, standby; With gelatin: glycerol: distilled water: antiseptic (mud pool tortoise beetle ester and mud are moored golden propyl ester)=1.1: 0.2: 1.1: 0.001 preparation capsule material, compacting promptly getting soft capsule.
Embodiments of the invention 10: 3 parts of 6 parts of Herba Polygoni Orientaliss, 5 parts of Folium Crataegi, 4 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi add 15 times of water gagings and decoct 4 times, each 2 hours, filter, merging filtrate, be evaporated to relative density 1.15, add ethanol and make and contain alcohol amount and reach 80%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.15, adds the suitable quantity of water dilution, 1: 20 AB-8 macroporous adsorptive resins of last blade diameter length ratio, absorption flow velocity 3BVh -1, discard and penetrate liquid, with 5BV washing, flow velocity 3BVh -1, discard water lotion, continuing and using 5BV55% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 3BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out the reduced vacuum drying, is ground into fine powder, gets extract; Radix Notoginseng adds 15 times of water gagings and decocts 4 times, each 3 hours, filters, merging filtrate is evaporated to 50 ℃ of relative densities 1.15, adds ethanol and makes and contain alcohol amount and reach 80%, stir, left standstill sucking filtration, decompression filtrate recycling ethanol 12 hours, and be concentrated into relative density 1.15, add the suitable quantity of water dilution, 1: 20 AB-8 macroporous adsorptive resins of last blade diameter length ratio, absorption flow velocity 3BVh -1, discard and penetrate liquid, with 5BV washing, flow velocity 3BVh -1, discard water lotion, continuing and using 5BV55% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 3BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out the reduced vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 4, use supercritical carbon dioxide extraction, is that 60MP, temperature are that 60 ℃, flow are the condition extraction 6h of 70L/h with pressure, resolves pressure 20MP, 60 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, mix homogeneously, in medicated powder: the ratio of substrate (poloxamer)=1: 2 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 75 ℃ of insulations down, splash in the middle of the condensed fluid (dimethicone and liquid Paraffin) with 40 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly get drop pill.
Embodiments of the invention 11: 4 parts of 8 parts of Herba Polygoni Orientaliss, 7 parts of Folium Crataegi, 6 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi add 12 times of water gagings and decoct 2 times, each 1.5 hours, filter merging filtrate, be evaporated to relative density 1.08, add ethanol and make and contain alcohol amount and reach 50%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.10, adds the suitable quantity of water dilution, 1: 15 DA of last blade diameter length ratio 201Macroporous adsorptive resins, absorption flow velocity 1BVh -1, discard and penetrate liquid, with 3BV washing, flow velocity 1BVh -1, discard water lotion, continuing and using 1BV40% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 1BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Radix Notoginseng adds 12 times of water gagings and decocts 2 times, each 1 hour, filters, merging filtrate, be evaporated to 50 ℃ of relative densities 1.08, add ethanol and make and contain alcohol amount and reach 50%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol, and be concentrated into relative density 1.10, add the suitable quantity of water dilution, 1: 15 DA of last blade diameter length ratio 201Macroporous adsorptive resins, absorption flow velocity 1BVh -1, discard and penetrate liquid, with 3BV washing, flow velocity 1BVh -1, discard water lotion, continuing and using 1BV40% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 1BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 2, use supercritical carbon dioxide extraction, is that 15MP, temperature are that 30 ℃, flow are the condition extraction 2h of 50L/h with pressure, resolves pressure 15MP, 25 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, mix homogeneously, in medicated powder: the ratio of substrate (glyceryl monostearate and insect wax)=1: 1 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 70 ℃ of insulations down, splash in the middle of the condensed fluid (liquid Paraffin and vegetable oil) with 20 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly get drop pill.
Embodiments of the invention 12: 5 parts of 10 parts of Herba Polygoni Orientaliss, 8 parts of Folium Crataegi, 7 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi add 8 times of water gagings and decoct 3 times, each 0.5 hour, filter merging filtrate, be evaporated to relative density 1.12, add ethanol and make and contain alcohol amount and reach 35%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.12, adds the suitable quantity of water dilution, 1: 5 D of last blade diameter length ratio 3520Macroporous adsorptive resins, absorption flow velocity 4BVh -1, discard and penetrate liquid, with 8BV washing, flow velocity 4BVh -1, discard water lotion, continuing and using 8BV85% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 4BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out lyophilization, is ground into fine powder, gets extract; Radix Notoginseng adds 8 times of water gagings and decocts 3 times, each 4 hours, filters, merging filtrate, be evaporated to 50 ℃ of relative densities 1.05, add ethanol and make and contain alcohol amount and reach 35%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol, and be concentrated into relative density 1.12, add the suitable quantity of water dilution, 1: 5 D of last blade diameter length ratio 3520Macroporous adsorptive resins, absorption flow velocity 4BVh -1, discard and penetrate liquid, with 8BV washing, flow velocity 4BVh -1, discard water lotion, continuing and using 8BV85% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 4BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out lyophilization, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 3, use supercritical carbon dioxide extraction, is that 40MP, temperature are that 40 ℃, flow are the condition extraction 8h of 90L/h with pressure, resolves pressure 25MP, 50 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, mix homogeneously, in medicated powder: the ratio of substrate (sodium stearate, poloxamer and insect wax)=1: 3 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 80 ℃ of insulations down, splash in the middle of the condensed fluid (dimethicone and vegetable oil) with 60 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly get drop pill.
Embodiments of the invention 13: 8 parts of 2 parts of Herba Polygoni Orientaliss, 4 parts of Folium Crataegi, 6 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 10 times of water gagings and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to relative density 1.10, add ethanol and make and contain alcohol amount and reach 65%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.07, adds the suitable quantity of water dilution, 1: 10 D of last blade diameter length ratio 101Macroporous adsorptive resins, absorption flow velocity 2BVh -1, discard and penetrate liquid, with 1BV washing, flow velocity 2BVh -1, discard water lotion, continuing and using 3BV70% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 2BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out microwave vacuum drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 3, use supercritical carbon dioxide extraction, is that 30MP, temperature are that 50 ℃, flow are the condition extraction 4h of 20L/h with pressure, resolves pressure 10MP, 40 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, adds an amount of mixing of starch again, granulate, and drying, granulate incapsulates, and promptly gets capsule.
Embodiments of the invention 14: 5 parts of 5 parts of Herba Polygoni Orientaliss, 5 parts of Folium Crataegi, 5 parts of Radix Notoginseng and Rhizoma Chuanxiongs
Herba Polygoni Orientalis, Folium Crataegi add 10 times of water gagings and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to relative density 1.10, add ethanol and make and contain alcohol amount and reach 65%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol also is concentrated into relative density 1.07, adds the suitable quantity of water dilution, 1: 10 DB of last blade diameter length ratio 301Macroporous adsorptive resins, absorption flow velocity 2BVh -1, discard and penetrate liquid, with 1BV washing, flow velocity 2BVh -1, discard water lotion, continuing and using 3BV70% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 2BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Radix Notoginseng adds 10 times of water gagings and decocts 3 times, each 2 hours, filters, merging filtrate, be evaporated to 50 ℃ of relative densities 1.10, add ethanol and make and contain alcohol amount and reach 65%, stir, left standstill 12 hours, sucking filtration, decompression filtrate recycling ethanol, and be concentrated into relative density 1.07, add the suitable quantity of water dilution, 1: 10 DB of last blade diameter length ratio 301Macroporous adsorptive resins, absorption flow velocity 2BVh -1, discard and penetrate liquid, with 1BV washing, flow velocity 2BVh -1, discard water lotion, continuing and using 3BV70% ethanol elution, eluting solvent is C1~C4 level alcohol, flow velocity 2BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out spray drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve No. 3, use supercritical carbon dioxide extraction, is that 30MP, temperature are that 50 ℃, flow are the condition extraction 4h of 20L/h with pressure, resolves pressure 10MP, 40 ℃ of temperature, and the collection extract is promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, adds mannitol and aspartame again, and mixing is made granule, and drying promptly gets granule.
The available arene of vegetable oil (a kind of or several miscella of soybean oil, Oleum Arachidis hypogaeae semen, Oleum Camelliae), organic acid, glycerol, isopropyl alcohol or surfactant used in the foregoing description replace.

Claims (10)

  1. [claim 1] a kind of Chinese medicine preparation for the treatment of angina pectoris is characterized in that: calculate according to composition by weight: it is prepared from drop pill, capsule, granule, soft capsule for 1~10 part by 1~10 part of Herba Polygoni Orientalis, 1~10 part of Folium Crataegi, 1~10 part of Radix Notoginseng and Rhizoma Chuanxiong.
  2. [claim 2] is characterized in that according to the Chinese medicine preparation of the described treatment angina pectoris of claim 1: calculate according to composition by weight: it is prepared from soft capsule or drop pill for 3 parts by 5 parts of Herba Polygoni Orientaliss, 4 parts of Folium Crataegi, 3 parts of Radix Notoginseng and Rhizoma Chuanxiong.
  3. [claim 3] treats the preparation method of the Chinese medicine preparation of angina pectoris as claimed in claim 1 or 2, it is characterized in that: Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng decoct with water, and filtrate concentrates, add ethanol and make and contain alcohol amount and reach 20~90%, leave standstill, filtrate recycling ethanol also concentrates, thin up, last macroporous adsorptive resins washes with water earlier, discard water lotion, continue, collect eluent with 20~95% ethanol elutions, reclaim ethanol, be condensed into thick paste, residue carries out drying, be ground into fine powder, get extract; The Rhizoma Chuanxiong pulverizing medicinal materials is used supercritical carbon dioxide extraction, collects extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
  4. [claim 4] is according to the preparation method of the Chinese medicine preparation of the described treatment angina pectoris of claim 3, it is characterized in that: Herba Polygoni Orientalis, Folium Crataegi, Radix Notoginseng add 5~20 times of water gagings and decoct 1~5 time, each 0.5~3 hour, filter, merging filtrate, be evaporated to relative density 1.02~1.20, adding ethanol makes and contains alcohol amount and reach 20~90%, stir, left standstill sucking filtration 12 hours, decompression filtrate recycling ethanol also is concentrated into relative density 1.05~1.20, add the suitable quantity of water dilution, the macroporous adsorptive resins of last blade diameter length ratio 1: 2~25, absorption flow velocity 0.5~5BVh -1, discard and penetrate liquid, with 0.5~10BV washing, flow velocity 0.5~5BVh -1, discard water lotion, continue with 0.5~10BV20~95% ethanol elution, flow velocity 0.5~5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve 1~No. 5, uses supercritical carbon dioxide extraction, with pressure is that 5~80MP, temperature are that 15~80 ℃, flow are condition extraction 0.5~10h of 5~100L/h, resolve pressure 5~30MP, 15~80 ℃ of temperature are collected extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
  5. [claim 5] treats the preparation method of the Chinese medicine preparation of angina pectoris as claimed in claim 1 or 2, it is characterized in that: Herba Polygoni Orientalis, Folium Crataegi decoct with water, and filter merging filtrate, concentrating under reduced pressure adds ethanol and makes and contain alcohol amount and reach 20~90%, leaves standstill, filtrate recycling ethanol also concentrates thin up, last macroporous adsorptive resins, wash with water earlier, discard water lotion, continue with 20~95% ethanol elutions, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder
    Get extract; Radix Notoginseng decocts with water, and filters merging filtrate, concentrating under reduced pressure, add ethanol and make and contain alcohol amount and reach 20~90%, leave standstill sucking filtration, decompression filtrate recycling ethanol also concentrates thin up, last macroporous adsorptive resins, wash with water earlier, discard water lotion, continue with 20~95% ethanol elutions, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; The Rhizoma Chuanxiong pulverizing medicinal materials is used supercritical carbon dioxide extraction, collects extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
  6. [claim 6] is according to the preparation method of the Chinese medicine preparation of the described treatment angina pectoris of claim 5, it is characterized in that: Herba Polygoni Orientalis, Folium Crataegi add 5~20 times of water gagings and decoct 1~5 time, each 0.5~3 hour, filter, merging filtrate, be evaporated to relative density 1.05~1.20, adding ethanol makes and contains alcohol amount and reach 20~90%, stir, left standstill sucking filtration 12 hours, decompression filtrate recycling ethanol also is concentrated into relative density 1.05~1.20, add the suitable quantity of water dilution, the macroporous adsorptive resins of last blade diameter length ratio 1: 2~25, absorption flow velocity 0.5~5BVh -1, discard and penetrate liquid, with 0.5~10BV washing, flow velocity 0.5~5BVh -1, discard water lotion, continue with 0.5~10BV20~95% ethanol elution, flow velocity 0.5~5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Radix Notoginseng adds 5~20 times of water gagings and decocts 1~5 time, each 0.5~5 hour, filters, merging filtrate is evaporated to 50 ℃ of relative densities 1.02~1.20, adds ethanol and makes and contain alcohol amount and reach 20~90%, stir, left standstill sucking filtration, decompression filtrate recycling ethanol 12 hours, and be concentrated into relative density 1.05~1.20, add the suitable quantity of water dilution, the macroporous adsorptive resins of last blade diameter length ratio 1: 2~25, absorption flow velocity 0.5~5BVh -1, discard and penetrate liquid, with 0.5~10BV washing, flow velocity 0.5~5BVh -1, discard water lotion, continue with 0.5~10BV20~95% ethanol elution, flow velocity 0.5~5BVh -1, collect eluent, reclaim ethanol, be condensed into thick paste, residue carries out drying, is ground into fine powder, gets extract; Rhizoma Chuanxiong pulverizing medicinal materials powdered is crossed sieve 1~No. 5, uses supercritical carbon dioxide extraction, with pressure is that 5~80MP, temperature are that 15~80 ℃, flow are condition extraction 0.5~10h of 5~100L/h, resolve pressure 5~30MP, 15~80 ℃ of temperature are collected extract promptly; The Rhizoma Chuanxiong extract adds aforementioned extract, and mix homogeneously adds suitable adjuvant then and makes different preparations.
  7. [claim 7] is according to the preparation method of the Chinese medicine preparation of claim 1 or 2 described treatment angina pectoris, it is characterized in that: the drop pill in the described preparation prepares like this: behind the extract obtained mix homogeneously, in medicated powder: the ratio of substrate=1: 1~3 feeds intake, and earlier with after the substrate fusion, adds the medicated powder mixing, 70~80 ℃ of insulations down, splash in the middle of the condensed fluid with 20~60 droplets/minute speed, drop pill is collected in the condensation molding, absorb condensed fluid with filter paper, promptly; Used substrate is one or more the mixture in Polyethylene Glycol-6000 or Polyethylene Glycol-400, polyoxyethylene monostearate, sodium stearate, poloxamer, stearic acid, glyceryl monostearate, the insect wax.
  8. [claim 8] is characterized in that according to the preparation method of the Chinese medicine preparation of claim 4 or 6 described treatment angina pectoris: used macroporous adsorptive resins model can be D 101, AB-8, DA 201, D 3520, D 4006, D 4020, DB 301Or X-5.
  9. [claim 9] is characterized in that according to the preparation method of the Chinese medicine preparation of claim 4 or 6 described treatment angina pectoris: described drying can adopt microwave vacuum drying, reduced vacuum drying, spray drying or lyophilization.
  10. [claim 10] is characterized in that according to the preparation method of the Chinese medicine preparation of the described treatment angina pectoris of claim 7: used condensed fluid is dimethicone, liquid Paraffin, vegetable oil or their mixture.
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