CN102389452B - Pharmaceutical composition for increasing heart coronary flow - Google Patents
Pharmaceutical composition for increasing heart coronary flow Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition for increasing heart coronary flow. The pharmaceutical composition is prepared from chrysanthemum total flavone and pfaffia pedersen total saponins in a mass ratio of 1:1, wherein the chrysanthemum total flavone contains no less than 85% of total flavone (determined by a UV method) and no less than 0.4% of luteolin-7-O-D-glucoside (determined by an HPLC method ); and pfaffia pedersen total saponins contains no less than 80% of total flavone (determined by a UV method). The invention can obviously increase rat in vitro heart coronary flow.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for increasing heart coronary flow.
Background technology
Flos Chrysanthemi is feverfew Chrysanthemummorifoliumat.) dry capitulum of Tzvel.The Dendranthema whole world has more than 30 to plant, about 17 kinds of China, but the cultivation hyoscine mainly is that Flos Chrysanthemi is a kind of, medicinal monoid is through long-term artificial culture selection-breeding and different ecological environmenies, in addition special processing method, formed the medicinal kind that differs from one another, such as Flos Chrysanthemi, milli chrysanthemum, Flos Chrysanthemi, Flos Chrysanthemi, Flos Chrysanthemi, Flos Chrysanthemi, Flos Chrysanthemi, Herba Tagetis Patulae etc.Flos Chrysanthemi is conventional Chinese medicine, has dispelling wind, and heat clearing away makes eye bright, detoxicating functions.Be used for the treatment of clinically hypertension and coronary heart disease.The main active of Flos Chrysanthemi is volatile oil and flavones ingredient, and the content of the total flavones in the Flos Chrysanthemi is high.Pharmacological research shows that the Flos Chrysanthemi crude extract has antibiotic, antiinflammatory, analgesia, antiviral, defying age, antitumor, antimutagenic, anti-liver lipid peroxidation, strengthens the multiple pharmacological effect such as immunologic function.But chrysanthemum total flavone (content of total flavones is not less than 85%) has no report as active ingredient for increasing the pharmacologically active of isolated rat coronary flow.
The Fa Feiya ginseng is Chinese mugwort Amaranthaceae (Amaranthaceae) genus Pfaffia (PfaffiaPedersen) plant, mainly grow in Amazon Basin, the botany record was arranged in 1826 first, the effects such as tonifying YANG, calmness, antitumor, treatment ulcer, rheumatic arthritis and blood sugar lowering are arranged.Fa Feixi contains several amino acids and vitamin, trace mineral comprises ferrum, magnesium, cobalt, silicon, the germanium of zinc and high-load, contain the saponin constituent that surpasses its dry weight 11%, comprise Fa Feixi acid (pfaffic acid) and glycoside thereof (such as Fa Feixi glycosides pfaffosides A-F), triterpenes (nortriperpene) and glycoside thereof, ecdysteroid parahormone (such as ecdysterone ecdysterone), pterosterone (pterosterone), foot sterone (podecdysone), stigmasterol (stigmasterol), sitosterol (sitostero) and glycoside thereof etc.Bibliographical information pfaffia crude extract has the pharmacological actions such as antitumor, tonifying YANG, the effect to blood system, antiinflammatory, analgesia work.But Fa Feiya ginseng total saponins (flavones content is not less than 80%) has no report as active ingredient for increasing the pharmacologically active of isolated rat coronary flow.
The effective site of known multiple Chinese medicine such as Radix Notoginseng, Radix Salviae Miltiorrhizae, Radix Puerariae, Rhizoma Chuanxiong, breviscapine etc. can produce the effect for the treatment of coronary heart disease from improving many-sided mechanism such as cardiac hemodynamic, hemorheology, adjusting vaso-active substance and calcium balance, protective wire plastochondria, removing free radical, promotion angiogenesis; and obtained good clinical effectiveness; prompting Chinese medicine has the advantages that to play a role at different levels, different target spot, provides new thinking for further developing the new Chinese medicine with treatment coronary heart disease.From document, the pharmacological research of Effective Component of Chinese Medicine anti-experimental character myocardial ischemia adopts single medicinal material effective site more at present, seldom carries out the research of Chinese medicine compound effective site.Therefore but Chinese medicine is used as medicine mainly with compound recipe clinically, develops the active component composition of herbal mixture treatment coronary heart disease, and carries out the research of mechanism of action, is the important directions of study of tcm new drug from now on, has great importance.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition having good pharmacologically active aspect the increase heart coronary flow.
The present invention by be chrysanthemum total flavone and Fa Feiya the ginseng total saponins formulated by 1: 1 weight ratio.
Above-mentioned chrysanthemum total flavone source has two, one, extracts with conventional alcohol heat reflux, and the self-control of purification with macroreticular resin method, the 2nd, be purchased.No matter be to make by oneself or be purchased, the content of its total flavones is not less than 85% (UV method mensuration) in the chrysanthemum total flavone, and luteolin-7-O-D-glucoside is not less than 0.4% (HPLC method mensuration).
Above-mentioned Fa Feiya ginseng total saponins source has two, one, adopts conventional alcohol heat reflux to extract, the self-control of purification with macroreticular resin method, and the 2nd, be purchased.No matter be to make by oneself or be purchased, its total saponin content is not less than 80% (UV method mensuration) in the Fa Feiya ginseng total saponins.
The present invention carries out rational compatibility with chrysanthemum total flavone and Fa Feiya ginseng total saponins, make two kinds of active ingredient synergism, the present invention of zoopery proof can obviously increase the isolated rat coronary flow, thereby provides a kind of new pharmaceutical composition for increasing heart coronary flow for people.
The specific embodiment
1. from the preparation of pharmacy
1.1 the preparation of chrysanthemum total flavone:
Get Jiangsu and produce Flos Chrysanthemi, the concentration that pulverize to add 10 times of amounts (times of weight) is the alcohol reflux 2 times of 70% (v/v): 6 times and 4 times, each 2 hours, merge extractive liquid,, reclaiming solvent to relative density is 1.2 fluid extracts, thin up becomes every milliliter of suitable 0.2g crude drug, filters filtrate for later use (recording general flavone content is 15.07mg.mL-1); Through pretreated AB-8 macroporous adsorbent resin, wet method dress post, the dress column volume is 100mL (weight in wet base 66g, dry weight 18g), blade diameter length ratio is 1: 8, the accurate upper prop liquid 400mL upper prop of drawing, coutroi velocity is 6mL/min.Use respectively 20% (v/v) ethanol elution impurity of 3 times of cylinder accumulated amount purified water and 1 times of cylinder accumulated amount, coutroi velocity is 6mL/min again, uses 60% ethanol (v/v) the eluting chrysanthemum total flavone of 3 times of cylinder accumulated amounts again, and coutroi velocity is 6mL/min.Collect eluent, concentrating under reduced pressure, vacuum drying namely get chrysanthemum total flavone to constant weight.General flavone content 85% (UV method mensuration); Luteolin-7-O-D-glucoside 0.4% (HPLC method mensuration).
1.2 the preparation of Fa Feiya ginseng total saponins:
Domestic Fa Feiya ginseng was pulverized 60 mesh sieves, and the concentration that adds 10 times of amounts (times of weight) is the ethanol of 70% (v/v), and hot reflux is extracted twice, each 1 hour, extracting solution let cool, and filtered, filtrate recycling ethanol is to distinguishing the flavor of without alcohol, and thin up becomes every milliliter of 0.2g crude drug, and this is upper prop liquid.
With the macroporous adsorbent resin PHD100 that the processed pillar of packing into, the pillar blade diameter length ratio is 1: 5, the upper prop liquid upper prop of resin volume will be three times in, coutroi velocity is three times of resin volumes per hour, after using again the deionized water eluting impurity of three times of resinite accumulated amounts, use again three times of resinite accumulated amounts 70% (v/v) ethanol elution, collect ion exchange resin column D941 (this exchanger resin column volume is identical with front pillar) on the ethanol elution, collected post liquid, using 70% ethanol (v/v) to be eluted to acetic anhydride-strong sulfuric acid response is negative again, merged post liquid and eluent, concentrating under reduced pressure, vacuum drying is to constant weight, and total saponins, total saponin content 80% (UV method mensuration) are joined in the luxuriant and rich with fragrance Asia of namely doing in the proper way.
1.3 undertaken composite by 1: 1 weight ratio above-mentioned chrysanthemum total flavone and Fa Feiya ginseng total saponins.
1.4 among the every 100mg of aforementioned pharmaceutical compositions, contain chrysanthemum total flavone and be not less than 40mg (being equivalent to Flos Chrysanthemi crude drug 1.60g), Fa Feiya ginseng total saponins is not less than 40mg (being equivalent to Fa Feiya ginseng crude drug 0.85g).
2 buy the preparation of medicine
2.1 chrysanthemum total flavone is purchased from Shanghai Mai Dipu pharmaceutcal corporation, Ltd, the content of total flavones is not less than 85% (UV method mensuration), and luteolin-7-O-D-glucoside is not less than 0.4% (HPLC method mensuration).
2.2 Fa Feiya joins total saponins, is purchased from China Medical Sciences Academy Medical Plants Institute's Guangxi branch, its total saponin content is not less than 80% (UV method mensuration).
2.3 undertaken composite by 1: 1 weight ratio above-mentioned chrysanthemum total flavone and Fa Feiya ginseng total saponins.
3. pharmaceutical composition of the present invention increases the experiment of isolated rat coronary flow effect
3.1 experiment material
3.1.1 experimental apparatus and reagent
Powerlab/8sp Langendorff isolated heart perfusion system, ADInstrument Pty Ltd (Australia).Krebs-Henseleit liquid, it consists of (mmol/L): NaCl 118, and KCl 4.7, and MgSO47H2O 1.2, and CaCl2 2.0, and NaHCO3 20, and KH2PO4 1.2, and Glucose 11.1, pH value 7.2-7.4.
3.1.2 tested medicine and preparation
Two kinds of drugs represent with numbering A and B respectively in following form, are provided by Yancheng, Jiangsu Province health professional technical college drug application institute.
A represents chrysanthemum total flavone, its preparation method: Jiangsu is produced the Flos Chrysanthemi alcohol heat reflux and is extracted, and purification with macroreticular resin, general flavone content are not less than 85% (UV method mensuration); Luteolin-7-O-D-glucoside is not less than 0.4% (HPLC method mensuration), the commercially available product that a representative is bought.
The luxuriant and rich with fragrance inferior ginseng total saponins of B method of representatives, its preparation method: the luxuriant and rich with fragrance inferior ginseng alcohol heat reflux of domestic cultivation extracts, and purification with macroreticular resin, total saponin content are not less than 80% (UV method mensuration).The commercially available product that the b representative is bought.
Be made into each desired concn with physiological saline solution before using:
Experiment prodrug A, B are made into A with Krebs-Henseleit liquid: B is respectively 10mg: the medicinal liquid of 10mg/ml, 6.66mg: 13.33mg/ml, 5mg: 15mg/ml, 13.33mg: 6.66mg/ml, 15mg: 5mg/ml, 20mg: 0mg/ml, 0mg: 20mg/ml, by A: B is respectively 2mg: 2mg, 1.33mg: 2.66mg, 1mg: 3mg, 2.66mg: 1.33mg, 3mg: 1mg, 4mg: 0mg, 0mg: the administration of 4mg/ heart, administration volume are 0.2ml.
3.1.3 laboratory animal
Healthy Wistar rat, male, body weight 350g ± 30g, Beijing Vital River Experimental Animals Technology Co., Ltd. provides.
3.2. experimental technique
3.2.1 group technology
Experiment is divided into medicine A group, medicine B group and A+B medicine group, and A+B medicine group comprises 1: 1 proportioning group, 1: 2 proportioning group, 1: 3 proportioning group, 2: 1 proportioning groups, 3: 1 proportioning groups.Establish altogether 7 groups, 14 every group rats (in table 2 and table 3, representing with n).Group technology, drug dose and administration concentration see Table 1.
Table 1 experiment group technology
3.2.2 Examination on experimental operation
The rat sacrificed by decapitation is taken out rapidly heart, places 4 ℃ of K-H liquid, discharges gently remained blood, and heart is connected to perfusion device and fixing, the beginning perfusion, and perfusate is kept 37 ℃, and passes into 95% oxygen.After electrocardio is steady, perfusion pressure is adjusted in 60-70mmHg carries out the voltage stabilizing perfusion, coronary flow before the administration of stable rear record slowly injects the medicinal liquid that the 0.2ml/ heart prepares through dosing holes, the above-mentioned indices of the complete rear immediate record of administration, the lasting observation 6 minutes.
3.2.3 detection index
Injection pressure (mmHg); Heart rate (inferior/minute); Before the administration and after the administration at once, 1,2,3,4,5 minute coronary flow (ml/min), coronary flow rate of change (%).
3.2.4 statistical procedures
Data mean ± standard deviation
The SPSS10.0 statistical software is adopted in expression, and rate of change relatively adopts one-way ANOVA to analyze between group, and the front and back measured value adopts paired t-test, and P＜0.05 is for there being significant difference.
3.3. result
3.3.1 respectively organize medicine to the impact of isolated rat heart heart rate
Before the experiment perfusion pressure is adjusted in 60-70mmHg and carries out the voltage stabilizing perfusion, medicine does not make significant difference to the isolated rat heart heart rate, the results are shown in Table 2.
Respectively organize isolated rat heart injection pressure, heart rate before and after table 2 administration
3.3.2 respectively organize medicine to the impact of coronary flow
Coronary flow there was no significant difference (P＞0.05) between each group before the administration; Respectively organizing the isolated rat heart coronary flow after the administration all has in various degree rising, and compares before the administration, and difference has statistical significance (P＜0.05 or P＜0.01); Each proportioning group has been compared significant difference (P＜0.05 or P＜0.01) after the administration with alone medicine A, B, and 1: 1 proportioning group of A+B medicine has the trend that is better than other group; Come to the same thing between self-control group and commercially available group.The results are shown in Table 3.
3.4. conclusion
By chrysanthemum total flavone A and the Fa Feiya ginseng total glycosides B pharmaceutical composition of the compatibility isolated rat heart coronary flow that can obviously raise by a certain percentage, in 5 proportionings (1: 1,1: 2,1: 3,2: 13: 1) group of different proportion, take the effect of 1: 1 proportioning group as excellent, fabricated material is identical by 1: 1 composite product effect with the marketable material preparation.
Table 3 medicine A+B is on the impact of isolated rat heart coronary flow (ml/min)
Annotate: 1, numerical value is rate of change (%) in the bracket; 2, respectively organize the front comparison of coronary flow measured value and administration:
*P＜0.05
*P＜0.01; 3, the rate of change of each group and alone medicine A group relatively
#P＜0.05
##P＜0.01; 4, the rate of change of each group and alone medicine B group relatively
▲P＜0.05
▲ ▲P＜0.01.
Claims (1)
1. chrysanthemum total flavone and Fa Feiya ginseng total saponins is pressed the formulated application of pharmaceutical composition in the medicine of preparation treatment increase heart coronary flow of weight ratio of 1:1;
The content of total flavones is not less than 85% in the aforementioned chrysanthemum total flavone, and luteolin-7-O-D-glucoside is not less than 0.4%, adopts following method preparation:
Get Jiangsu and produce Flos Chrysanthemi, pulverize the v/v concentration that adds 10 times of times of weight and be 70% alcohol reflux 2 times: 6 times and 4 times, each 2 hours, merge extractive liquid,, reclaiming solvent to relative density is 1.2 fluid extracts, thin up becomes every milliliter of suitable 0.2g crude drug, filter filtrate for later use; Through pretreated AB-8 macroporous adsorbent resin, wet method dress post, the dress column volume is 100mL, weight in wet base 66g, dry weight 18g, blade diameter length ratio are 1:8, accurate absorption upper prop liquid 400mL upper prop coutroi velocity is 6 mL/min; Be 20% ethanol elution impurity with the v/v concentration of 3 times of cylinder accumulated amount purified water and 1 times of cylinder accumulated amount respectively again, coutroi velocity is 6 mL/min, and the v/v concentration with 3 times of cylinder accumulated amounts is 60% ethanol elution chrysanthemum total flavone again, and coutroi velocity is 6 mL/min; Collect eluent, concentrating under reduced pressure, vacuum drying namely get chrysanthemum total flavone to constant weight;
Fa Feiya ginseng total saponin content is not less than 80%, adopts following method preparation:
Domestic Fa Feiya ginseng was pulverized 60 mesh sieves, and the v/v concentration that adds 10 times of times of weight is 70% ethanol, and hot reflux extracts twice, and each 1 hour, extracting solution let cool, and filters, and filtrate recycling ethanol is to nothing alcohol flavor, and thin up becomes every milliliter of 0.2g crude drug, and this is upper prop liquid; With the macroporous adsorbent resin PHD100 that the processed pillar of packing into, the pillar blade diameter length ratio is 1:5, the upper prop liquid upper prop of resin volume will be three times in, coutroi velocity is three times of resin volumes per hour, after using again the deionized water eluting impurity of three times of resinite accumulated amounts, v/v concentration with three times of resinite accumulated amounts is 70% ethanol elution again, collect ion exchange resin column D941 on the ethanol elution, this exchanger resin column volume is identical with front pillar, collects post liquid, is that 70% ethanol elution to acetic anhydride-strong sulfuric acid response is negative with v/v concentration again, merged post liquid and eluent, concentrating under reduced pressure, vacuum drying are to constant weight, and total saponins is joined in the luxuriant and rich with fragrance Asia of namely doing in the proper way.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101953869A (en) * | 2010-10-21 | 2011-01-26 | 盐城卫生职业技术学院 | Medicinal composition for resisting myocardial ischemia and hypoxia |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101953869A (en) * | 2010-10-21 | 2011-01-26 | 盐城卫生职业技术学院 | Medicinal composition for resisting myocardial ischemia and hypoxia |
Non-Patent Citations (4)
| Title |
|---|
| 大孔吸附树脂法纯化杭白菊总黄酮;闫克玉等;《现代食品科技》;20080131;第24卷(第1期);第35-38页 * |
| 法菲亚属植物化学成分和药理活性研究进展;高辉等;《中国中药杂志》;20061130;第31卷(第21期);第1749-1752页 * |
| 闫克玉等.大孔吸附树脂法纯化杭白菊总黄酮.《现代食品科技》.2008,第24卷(第1期),第35-38页. |
| 高辉等.法菲亚属植物化学成分和药理活性研究进展.《中国中药杂志》.2006,第31卷(第21期),第1749-1752页. |
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