CN1981817B - Chinese-medicinal composition for treating cardiovascular diseases, its preparation and use - Google Patents
Chinese-medicinal composition for treating cardiovascular diseases, its preparation and use Download PDFInfo
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- CN1981817B CN1981817B CN2005101223440A CN200510122344A CN1981817B CN 1981817 B CN1981817 B CN 1981817B CN 2005101223440 A CN2005101223440 A CN 2005101223440A CN 200510122344 A CN200510122344 A CN 200510122344A CN 1981817 B CN1981817 B CN 1981817B
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Abstract
A Chinese medicine for preventing and treating myocardial ischemia is prepared from the extract of red sage root (30-40 Wt%), the extract of tree peony bark (60-70 Wt%) and medicinal auxiliaries.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition for the treatment of cardiovascular disease; Relate in particular to the active component alkannic acid (Lithospermic acid) that from Radix Salviae Miltiorrhizae, extracts, salvianolic acid B (Salvianolic acid B), the active component paeonol glycoside (Paeonidanin) that extracts in salvianolic acid E (Salvianolic acid E) and the Cortex Moutan, the combination of paeonoside b (Mudanpioside b), the preparation that contains said composition, and have application in the anti-myocardial ischemia drugs with function in preparation.
Background technology
Coronary heart disease and angina pectoris are harm humans health " first killers ", in recent years, along with the variation of China's population senescence and people's work, life, dietary structure and environment etc., the incidence rate of cardiovascular and cerebrovascular diseases such as coronary heart disease also increases year by year, and the people's physical and mental health in serious threat.China rises to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven because of cardiovascular and cerebrovascular disease death person accounts for the percentage ratio of total dead population, and the person reaches 2,000,000 to die from the cardiovascular and cerebrovascular disease every year.
At present, there are a lot of Chinese medicines to be used for the treatment of cardiovascular and cerebrovascular disease, as decoction for removing blood stasis, FUFANG DANSHEN DIWAN etc.
Two folk prescriptions are made up of Radix Salviae Miltiorrhizae and Cortex Moutan, cure mainly type of obstruction of heart-blood obstruction of qi in the chest and cardialgia (ischemic heart desease).Ischemic heart desease belongs to Chinese medicine thoracic obstruction category, and patient's blood flow shows as the state that coagulates, glues, gathers, stagnates.Pathogenesis is a principal contradiction with blood stasis retardance heart network, and the heart is become homeless foster, and stagnation of QI and blood may bring about pain is so blood circulation promoting and blood stasis dispelling is first to want method.Two folk prescriptions base oneself upon and effect a permanent cure, and the mutual reinforcement between of Radix Salviae Miltiorrhizae Cortex Moutan is a usefulness, blood circulation promoting and blood stasis dispelling, and removing obstruction in the collateral to relieve pain just closes type of obstruction of heart-blood obstruction of qi in the chest and cardialgia pathogenesis.Have the merit that nourishes blood during Radix Salviae Miltiorrhizae is invigorated blood circulation again concurrently, invigorate blood circulation and just do not hinder, benefit is arranged in logical, complement each other.Two red granules are listed in the national spark project plan (00B101D7400035) in 2000 in listing in 1996.Pharmacological research shows: two folk prescription agent can significantly improve dog acute myocardial ischemia scope and degree of ischemia, reduce infarct size, significantly suppress the active and lactic acid dehydrogenase release of serum creatine phosphokinase, suppress platelet adhesion and aggregation, inhibition thrombosis; Coronary flow due to the pituitrin reduced obvious protective effect.
Chinese medicine has systemic characteristics by multipath, many target spots, integration regulatory mechanism performance drug action.But, the Chinese medicine complex chemical composition, effective substance is indeterminate, is difficult to quality control.The effect of the various effective ingredient in Chinese of treatment cardiovascular and cerebrovascular disease is had nothing in common with each other and is stressed, and with the full side of compatibility replacement of effective site, has both possessed the characteristics of Chinese medicine mass action, has reduced its complexity simultaneously, is convenient to the quality control of medicine.Therefore, provide convenient effective effective ingredient in Chinese compound preparation to have the important clinical meaning.
Summary of the invention
The purpose of this invention is to provide a kind of Chinese medicine active component compound for the treatment of cardiovascular disease.
Another object of the present invention provides the purposes of said composition.
The present invention also provides the preparation that contains said composition.
The present invention is implemented by the following technical programs:
Chinese medicine composition of the present invention is made up of Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, and the percentage by weight of each component is:
Radix Salviae Miltiorrhizae extract 30%～40%;
Cortex Moutan extract 60%～70%.
Preferably, the percentage by weight of each component is in the Chinese medicine composition of the present invention:
Radix Salviae Miltiorrhizae extract 31%～39%;
Cortex Moutan extract 61%～69%.
Preferred, the percentage by weight of each component is in the Chinese medicine composition of the present invention:
Radix Salviae Miltiorrhizae extract 32%～38%;
Cortex Moutan extract 62%～68%.
Best, the percentage by weight of each component is in the Chinese medicine composition of the present invention:
Radix Salviae Miltiorrhizae extract 33%～37%;
Cortex Moutan extract 63%～67%.
In the Chinese medicine composition of the present invention, the content of alkannic acid is 3～4% in the Radix Salviae Miltiorrhizae extract, and the content of salvianolic acid B is 92～94%, and the content of salvianolic acid E is 1～2%; The content of paeonol glycoside in the Cortex Moutan extract (Paeonidanin) is 20～30%, and the content of paeonoside b (Mudanpioside b) is 35～45%.
The preparation method of Chinese medicine composition of the present invention may further comprise the steps:
(1) preparation of Radix Salviae Miltiorrhizae extract: Radix Salviae Miltiorrhizae is pulverized the back add ethyl acetate and ethanol, heating extraction gets extracting solution I, abandons it.Medicinal residues add ethanol, heating extraction gets extracting solution II, II is condensed into extractum with extracting solution, use dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use low concentration methanol as mobile phase, get eluent I, change high concentration methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography; The separation condition of preparative hplc: chromatographic column is a semi-preparative column, and mobile phase is water and acetonitrile, gradient elution;
(2) preparation of Cortex Moutan extract: will add ethyl acetate and ethanol after the Cortex Moutan pulverizing medicinal materials, heating extraction gets extracting solution I, abandons it.Medicinal residues add ethanol, heating extraction gets extracting solution II, II is condensed into extractum with extracting solution, use dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use low concentration methanol as mobile phase, get eluent I, change high concentration methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography; The separation condition of preparative hplc: chromatographic column is a semi-preparative column, and mobile phase is water and acetonitrile, gradient elution;
(3) according to recipe quantity Radix Salviae Miltiorrhizae extract and Cortex Moutan extract are mixed.
Preferably, the preparation method of Chinese medicine composition of the present invention may further comprise the steps:
(1) preparation of Radix Salviae Miltiorrhizae extract: get red rooted salvia, it is pulverized the back add ethyl acetate and ethanol (1: 0.8～1.2), reflux 0.8～1.2 hour is extracted 1～3 time, and merging filtrate gets extracting solution I, abandons it.In medicinal residues, add 60%～80% ethanol, reflux 0.8～1.2 hour is extracted 1～3 time, filtrate merge extracting solution II, II is condensed into extractum with extracting solution, with 40%～60% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 3%～8% methanol as mobile phase, get eluent I, change 50%～70% methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography; The separation condition of preparative hplc: chromatographic column is a semi-preparative column, and mobile phase is water and acetonitrile, and gradient elution, flow velocity are 2.8～3.2ml/min, and column temperature is a room temperature;
(2) preparation of Cortex Moutan extract: will add ethyl acetate and ethanol (1: 0.8～1.2) after the Cortex Moutan pulverizing medicinal materials, reflux 0.8～1.2 hour is extracted 1～3 time, and merging filtrate gets extracting solution I, abandons it.In medicinal residues, add 60%～80% ethanol, reflux 0.8～1.2 hour is extracted 1～3 time, filtrate merge extracting solution II, II is condensed into extractum with extracting solution, with 40%～60% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 3%～8% methanol as mobile phase, get eluent I, change 50%～70% methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography; The separation condition of preparative hplc: chromatographic column is a semi-preparative column, and mobile phase is water and acetonitrile, and gradient elution, flow velocity are 2.8～3.2ml/min, and column temperature is a room temperature;
(3) according to recipe quantity Radix Salviae Miltiorrhizae extract and Cortex Moutan extract are mixed.
Best, the preparation method of Chinese medicine composition of the present invention is:
(1) preparation of Radix Salviae Miltiorrhizae extract: get red rooted salvia, it is pulverized the back add ethyl acetate and ethanol (1: 1), reflux 1 hour is extracted 2 times, filtrate merge extracting solution I.Medicinal residues add 70% ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution II, II is condensed into extractum with extracting solution, with 50% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 5% methanol as mobile phase, get eluent I, change 60% methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography: the separation condition of preparative hplc: chromatographic column is semi-preparative column (Lichrospher C18; 10.0mm * 250mm, 5 μ m), mobile phase is water (A) and acetonitrile (B), the gradient elution program is as follows: during 0min, mobile phase A is water+0.1% acetum of 85%, and Mobile phase B is 15% acetonitrile solution; During 10in, mobile phase A is water+0.1% acetum of 79%, and Mobile phase B is 21% acetonitrile solution; During 15min, mobile phase A is water+0.1% acetum of 69%, and Mobile phase B is 31% acetonitrile solution; During 30min, mobile phase A is water+0.1% acetum of 63%, and Mobile phase B is 37% acetonitrile solution; During 35min, mobile phase A is water+0.1% acetum of 15%, and Mobile phase B is 85% acetonitrile solution; During 45min, mobile phase A is water+0.1% acetum of 15%, and Mobile phase B is 85% acetonitrile solution; Flow velocity is 3ml/min, and column temperature is a room temperature; Sample 100% dissolve with ethanol separates through preparative liquid chromatography, collects solution at time period 17.5～23.6min, and solution obtains active component behind concentrate drying;
(2) preparation of Cortex Moutan extract: get the Cortex Moutan medical material, it is pulverized the back add ethyl acetate and ethanol (1: 1), reflux 1 hour is extracted 2 times, filtrate merge extracting solution I.Medicinal residues add 70% ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution II, II is condensed into extractum with extracting solution, with 50% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 5% methanol as mobile phase, get eluent I, change 60% methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography: the separation condition of preparative hplc: chromatographic column is semi-preparative column (the Lichrospher C18 of Chinese nation; 10.0mm * 250mm, 5 μ m), mobile phase is water (A) and acetonitrile (B), and the gradient elution program is as follows: in the time of 0 minute, mobile phase A is that 90% aqueous solution, Mobile phase B are 10% acetonitrile solution; In the time of 8 minutes, mobile phase A is that 81% aqueous solution, Mobile phase B are 19% acetonitrile solution; In the time of 60 minutes, mobile phase A is that 65% aqueous solution, Mobile phase B are 35% acetonitrile solution; Flow velocity is 3ml/min, and column temperature is a room temperature.Sample separates through preparative liquid chromatography with 1 00% dissolve with ethanol, collects solution at time period 7.7～10.7min, and solution obtains active component behind concentrate drying;
(3) according to percentage by weight, with Radix Salviae Miltiorrhizae extract 33%～37%, Cortex Moutan extract 63%～67% mixes.
Chinese medicine composition of the present invention can add adjuvant, makes any form on the pharmaceutics according to conventional preparation method.
Chinese medicine composition of the present invention can also have the ingredient compatibility of identical curative effect with other, makes any preparation of accepting on the pharmaceutics according to conventional method.
Described preparation comprises injection and oral formulations.Wherein injection comprises injection, drip liquid, injectable powder; Oral formulations comprises granule, tablet, electuary, powder, oral liquid, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, sucks agent, granule, pill, unguentum, sublimed preparation, spray, drop pill, disintegrating agent, oral cavity disintegration tablet, micropill etc.
Usefulness of the present invention is: Chinese medicine composition provided by the invention is the compositions of the effective ingredient that extracts from Radix Salviae Miltiorrhizae, Cortex Moutan medical material, the compare Chinese medicine of existing treatment cardiovascular and cerebrovascular disease, its chemical constituent is simply clear and definite, on pharmacological research, be easier to illustrate its mechanism of action, be easier to the quality control of medicine aborning.
Description of drawings
Fig. 1 is the HPLC analysis chart of Radix Salviae Miltiorrhizae extract of the present invention;
Fig. 2 is the HPLC analysis chart of Cortex Moutan extract of the present invention.
The experimental example and the specific embodiment below by medicine of the present invention are further set forth beneficial effect of the present invention, are intended to illustrate the present invention, but not are limitation of the present invention.
Experimental example one pharmacological evaluation
Former generation myocardial cell cultivation After 1～3 day SD neonatal rat that is born was put to death, it was dirty to core, and subtracts into 1mm after PBS liquid cleans
3About fragment.With 0.125% trypsin Sigma, USA)+0.05% (Gibco is USA) in 37 degree digestion 3～4 times for collagenase II.The differential adherent method was separated into fibrocyte after 1.5 hours, and cell suspension is transferred to (every hole about 4 * 10 in 48 orifice plates
5Cell).(Gibco, (Falcon, USA) cell of cultivating 3～6 days supplies medicine efficacy screening USA) to add 10% hyclone through DMEM.Screen and replaced with serum-free medium in preceding 1 day.Cultivate 3～6 days myocardial cell, PBS washing back adds the pastille culture fluid.Place 95%N
2And 5%CO
2Anoxia is 6 hours in the incubator.Then at CO
2Reoxygenation is 3 hours in the incubator.Get cell conditioned medium liquid and measure LDH content.
The lactic acid dehydrogenase assayLactic acid dehydrogenase content can be represented the cell injury degree in the cell culture fluid.The lactic acid dehydrogenase content that bleeds in the supernatant is high more, shows that cell injury is also remarkable.The determination of lactate dehydrogenase test kit builds up bio-engineering research institute available from Nanjing.Assay method is: get 30 microlitre cell conditioned medium liquid, add 50 microlitre substrate buffer and 10 microlitre lactic dehydrogenase enzyme cofactors, 37 degree vibrations 15 minutes add 50 microlitre 2,4 dinitrophenyl hydrazines again, 37 degree vibrations 15 minutes.Parallel blank.Extract reaction solution 50 microlitres and add 200 microlitre 0.4mol/L sodium hydroxide solutions, leave standstill 3～4 minutes after, measure shading value with microplate reader in 450nm.
Dosage regimenRadix Salviae Miltiorrhizae among the embodiment 1, Cortex Moutan extract compositions A, B, C, D, E are made into 10 with sugar-free Hanks liquid respectively
-4G/mL test liquid, liposoluble constituent can add a small amount of DMSO hydrotropy (the DMSO final concentration is controlled at below 0.2%).The final concentration of each component in culture fluid is controlled at 10
-5G/mL.
The resultAll data are represented with the mean value variance, adopt monolateral variance analysis and T check carrying out statistical analysis.Compare with model group, P＜0.05 is thought significantly effectively.Experimental result sees Table 1.
Table 1 Radix Salviae Miltiorrhizae, Cortex Moutan extract compositions are to the influence of neonatal rat myocardial cell lactic acid dehydrogenase
The present invention adopts neonatal rat myocardial cell anoxia reoxygenation model, by mensuration to lactic acid dehydrogenase, and the anti-myocardial ischemia effect of check Chinese medicine composition of the present invention.The result shows that the compositions of Radix Salviae Miltiorrhizae, Cortex Moutan extract has the highly significant effect to reducing lactic acid dehydrogenase release, illustrates that Chinese medicine composition of the present invention has the effect of tangible anti-myocardial ischemia.
Active constituent content measuring in experimental example two Radix Salviae Miltiorrhizae extracts of the present invention
(1) alkannic acid in the Radix Salviae Miltiorrhizae extract of the present invention (Lithospermic acid), salvianolic acid B (Salvianolic acid B), the assay (high performance liquid chromatography) of salvianolic acid E (Salvianolic acid E).
Chromatographic condition chromatographic column: Agilent Zorbax SB-C18 post (4.6mm * 150mm, 5 μ m); Adopt gradient elution, mobile phase A is 0.2% glacial acetic acid aqueous solution mutually, and Mobile phase B is mutually for containing the acetonitrile solution of 0.2% glacial acetic acid; The gradient elution program is as follows: in the time of 0 minute, mobile phase A is that 80% 0.2% glacial acetic acid aqueous solution, Mobile phase B are the acetonitrile solution of 20% 0.2% glacial acetic acid; In the time of 15 minutes, mobile phase A is that 50% 0.2% glacial acetic acid aqueous solution, Mobile phase B are the acetonitrile solution of 50% 0.2% glacial acetic acid; In the time of 20 minutes, mobile phase A is that 50% 0.2% glacial acetic acid aqueous solution, Mobile phase B are the acetonitrile solution of 50% 0.2% glacial acetic acid; Flow velocity 0.5mLmin-1; It is long to detect the wavelength all-wave; 30 ℃ of column temperatures; ELSD condition: nitrogen 1.8l/min, drift tube temperature: 105 ℃.
The preparation of need testing solution takes by weighing this product, in volumetric flask, is diluted to scale with dissolve with methanol solution, shakes up, promptly.
The accurate need testing solution of drawing of assay method injects chromatograph of liquid, measures, promptly.
(2) the HPLC-ELSD finger printing of above-mentioned Radix Salviae Miltiorrhizae extract
Assay method is referring to alkannic acid in (1) above-mentioned Radix Salviae Miltiorrhizae extract, salvianolic acid B, the assay of salvianolic acid E (high performance liquid chromatography).The record chromatograph time is 25 minutes.
The HPLC-ELSD analysis of spectra of analysis result Danshen effective component is seen Fig. 1, and 1,2, No. 3 peak among Fig. 1 is respectively an alkannic acid, salvianolic acid B, and salvianolic acid E, its content is respectively 3.56%, 93.02%, and 1.51%.
Active constituent content measuring in experimental example three Cortex Moutan extracts of the present invention
(1) assay (high performance liquid chromatography) of paeonol glycoside (Paeonidanin), paeonoside b (Mudanpioside b) in the Cortex Moutan extract of the present invention
Chromatographic condition chromatographic column Agilent Zorbax SB-C18 post (4.6mm * 150mm, 5 μ m); Adopt gradient elution, mobile phase A is 0.2% glacial acetic acid aqueous solution mutually, and Mobile phase B is mutually for containing the acetonitrile solution of 0.2% glacial acetic acid; The gradient elution program is as follows: in the time of 0 minute, mobile phase A is that 90% 0.2% glacial acetic acid aqueous solution, Mobile phase B are the acetonitrile solution of 10% 0.2% glacial acetic acid; In the time of 10 minutes, mobile phase A is that 70% 0.2% glacial acetic acid aqueous solution, Mobile phase B are the acetonitrile solution of 30% 0.2% glacial acetic acid; In the time of 30 minutes, mobile phase A is that 50% 0.2% glacial acetic acid aqueous solution, Mobile phase B are the acetonitrile solution of 50% 0.2% glacial acetic acid; Flow velocity 0.5mLmin-1; It is long to detect the wavelength all-wave; 30 ℃ of column temperatures; ELSD condition: 105 ℃ of drift tube temperatures; Nitrogen flow rate 1.8L/min
The preparation of need testing solution takes by weighing the about 1.83mg of this product, in dissolve with methanol solution 1ml volumetric flask, is diluted to scale, shakes up, promptly.
Accurate need testing solution 5 μ 1 that draw of assay method inject chromatograph of liquid, measure, promptly.
(2) above-mentioned Cortex Moutan extract HPLC-ELSD finger printing
Assay method is referring to the paeonol glycoside (Paeonidanin) in (1) above-mentioned Cortex Moutan extract, paeonoside b (Mudanpioside b) assay (high performance liquid chromatography).The record chromatograph time is 30 minutes.
The HPLC-ELSD analysis of spectra of analysis result moutan bark effective constituent is seen Fig. 2, and 1, No. 2 among Fig. 2 is respectively paeonol glycoside (Paeonidanin), paeonoside b (Mudanpioside b).The relative retention time at two peaks is followed successively by 3.82 (paeonol glycoside (Paeonidanin)), 4.78 (paeonoside b (Mudanpioside b)).
The content that the invention provides paeonol glycoside in the moutan bark effective constituent (Paeonidanin) is 20～30%, and the content of paeonoside b (Mudanpioside b) is 35～45%.
Paeonol glycoside of the present invention (Paeonidanin, the special formula of structure 9-O-methyl-4-one-albiflorin) is:
The special formula of the structure of paeonoside b of the present invention (Mudanpioside b) is:
The specific embodiment
Embodiment one
Get red rooted salvia 250g, it is pulverized the back add ethyl acetate and ethanol (1: 1), reflux 1 hour is extracted 2 times, filtrate merge extracting solution I.Medicinal residues add 70% ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution II, extracting solution II is condensed into extractum gets 138.3g, with 50% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 5% methanol as mobile phase, get eluent I, change 60% methanol then as mobile phase, get eluent II, get sample 13.83g behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography: the separation condition of preparative hplc: chromatographic column is semi-preparative column (Lichrospher C18; 10.0mm * 250mm, 5 μ m), mobile phase is water (A) and acetonitrile (B), the gradient elution program is as follows: during 0min, mobile phase A is water+0.1% acetum of 85%, and Mobile phase B is 15% acetonitrile solution; During 10in, mobile phase A is water+0.1% acetum of 79%, and Mobile phase B is 21% acetonitrile solution; During 15min, mobile phase A is water+0.1% acetum of 69%, and Mobile phase B is 31% acetonitrile solution; During 30min, mobile phase A is water+0.1% acetum of 63%, and Mobile phase B is 37% acetonitrile solution; During 35min, mobile phase A is water+0.1% acetum of 15%, and Mobile phase B is 85% acetonitrile solution; During 45min, mobile phase A is water+0.1% acetum of 15%, and Mobile phase B is 85% acetonitrile solution; Flow velocity is 3ml/min, and column temperature is a room temperature; Sample 100% dissolve with ethanol separates through preparative liquid chromatography, collects solution at time period 17.5～23.6min, and solution obtains active component 5.70g behind concentrate drying.
Get Cortex Moutan medical material 250g, it is pulverized the back add ethyl acetate and ethanol (1: 1), reflux 1 hour is extracted 2 times, filtrate merge extracting solution I.Medicinal residues add 70% ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution II, extracting solution II is condensed into extractum 55g, with 50% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 5% methanol as mobile phase, get eluent I, change 60% methanol then as mobile phase, get eluent II, get sample 26.48g behind the concentrate drying.Continue to separate the sample that obtains with preparative liquid chromatography.The separation condition of preparative hplc: chromatographic column is semi-preparative column (the Lichrospher C18 of Chinese nation; 10.0mm * 250mm, 5 μ m), mobile phase is water (A) and acetonitrile (B), and gradient sees Table 2, and flow velocity is 3ml/min, and column temperature is a room temperature.Sample 100% dissolve with ethanol separates through preparative liquid chromatography, collects solution at time period 7.7-10.7min, and solution obtains active component 1.83g behind concentrate drying.
Embodiment two
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3 * 10
-6Gram Radix Salviae Miltiorrhizae extract and 7 * 10
-6The gram Cortex Moutan extract mix mixture A.
Embodiment three
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.9 * 10
-6Gram Radix Salviae Miltiorrhizae extract and 6.1 * 10
-6The gram Cortex Moutan extract mix mixture B.
Embodiment four
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.2 * 10
-6Gram Radix Salviae Miltiorrhizae extract and 6.7 * 10
-6The gram Cortex Moutan extract mix mixture C.
Embodiment five
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.7 * 10
-6Gram Radix Salviae Miltiorrhizae extract and 6.3 * 10
-6The gram Cortex Moutan extract mix mixture D.
Embodiment six
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.4 * 10
-6Gram Radix Salviae Miltiorrhizae extract and 6.6 * 10
-6The gram Cortex Moutan extract mix mixture E.
Embodiment seven
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3 * 10
-2～4 * 10
-2Gram Radix Salviae Miltiorrhizae extract and 6 * 10
-2～7 * 10
-2Gram Cortex Moutan extract mixture F makes Radix Salviae Miltiorrhizae extract in the mixing account for 30%～40% of gross weight and accounts for 60%～70% of gross weight with Cortex Moutan extract.
Embodiment eight
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.1 * 10
-2～3.9 * 10
-2Gram Radix Salviae Miltiorrhizae extract and 6.1 * 10
-2～6.9 * 10
-2Gram Cortex Moutan extract mixture G makes Radix Salviae Miltiorrhizae extract in the mixing account for 31%～39% of gross weight and accounts for 61%～69% of gross weight with Cortex Moutan extract.
Embodiment nine
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.2 * 10
-2～3.8 * 10
-2Gram Radix Salviae Miltiorrhizae extract and 6.2 * 10
-2～6.8 * 10
-2Gram Cortex Moutan extract mixture H makes Radix Salviae Miltiorrhizae extract in the mixing account for 32%～38% of gross weight and accounts for 62%～68% of gross weight with Cortex Moutan extract.
Embodiment ten
Method extraction by embodiment one obtains Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, with 3.3 * 10
-2～3.7 * 10
-2Gram Radix Salviae Miltiorrhizae extract and 6.3 * 10
-2～6.7 * 10
-2Gram Cortex Moutan extract mixture I makes Radix Salviae Miltiorrhizae extract in the mixing account for 33%～37% of gross weight and accounts for 63%～67% of gross weight with Cortex Moutan extract.
Embodiment 11
Get the Danshen effective component 1g of embodiment one, moutan bark effective constituent 2g and 10.5g Polyethylene Glycol-6000 mix homogeneously, heating and melting moves in the drop pill drip irrigation behind the change material, and in ℃ liquid paraffin of medicine liquid droplet to 6～8, oil removing makes 600 of drop pill.
Get the Danshen effective component 1g of embodiment one, moutan bark effective constituent 2g, glucose 4.5g, sodium thiosulfate 0.9g and distilled water 1ml, behind the said components mix homogeneously, lyophilization, 800 of packing, promptly.
Embodiment 13
Get Lignum Dalbergiae Odoriferae oil 1.5g, join in the saturated hydroxypropyl of 13ml, stirring and dissolving filters, and the filtrate cold drying gets the clathrate powder of Lignum Dalbergiae Odoriferae oil and hydroxypropyl.Lignum Dalbergiae Odoriferae oil is closed the clathrate powder of hydroxypropyl, the Danshen effective component 1g of embodiment one, Cortex Moutan extract 2g, mannitol 5.5g, behind calcium disodium edetate 0.9g and the distilled water 2ml mixing, lyophilization, 500 of packing, promptly.
Claims (7)
1. a Chinese medicine composition for the treatment of cardiovascular disease is made up of Radix Salviae Miltiorrhizae extract and Cortex Moutan extract, it is characterized in that, the percentage by weight of each component is:
Radix Salviae Miltiorrhizae extract 30%～40%;
Cortex Moutan extract 60%～70%;
Described Radix Salviae Miltiorrhizae extract adopts following method preparation:
Get red rooted salvia, it is pulverized the back add 1: 1 ethyl acetate and ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution I; Medicinal residues add 70% ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution II, II is condensed into extractum with extracting solution, with 50% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 5% methanol as mobile phase, get eluent I, change 60% methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography: the separation condition of preparative hplc: chromatographic column is a semi-preparative column: Lichrospher C18; 10.0mm * 250mm, 5 μ m, mobile phase A is that water and B are acetonitrile, the gradient elution program is as follows: during 0min, mobile phase A is water+0.1% acetum of 85%, and Mobile phase B is 15% acetonitrile solution; During 10min, mobile phase A is water+0.1% acetum of 79%, and Mobile phase B is 21% acetonitrile solution; During 15min, mobile phase A is water+0.1% acetum of 69%, and Mobile phase B is 31% acetonitrile solution; During 30min, mobile phase A is water+0.1% acetum of 63%, and Mobile phase B is 37% acetonitrile solution; During 35min, mobile phase A is water+0.1% acetum of 15%, and Mobile phase B is 85% acetonitrile solution; During 45min, mobile phase A is water+0.1% acetum of 15%, and Mobile phase B is 85% acetonitrile solution; Flow velocity is 3ml/min, and column temperature is a room temperature; Sample 100% dissolve with ethanol separates through preparative liquid chromatography, collects solution at time period 17.5～23.6min, and solution obtains active component behind concentrate drying;
Described Cortex Moutan extract adopts following method preparation:
Get the Cortex Moutan medical material, it is pulverized the back add 1: 1 ethyl acetate and ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution I; Medicinal residues add 70% ethanol, reflux 1 hour is extracted 2 times, filtrate merge extracting solution II, II is condensed into extractum with extracting solution, with 50% dissolve with methanol extractum, adopt the ODS-C18 post that it is separated, at first use 5% methanol as mobile phase, get eluent I, change 60% methanol then as mobile phase, get eluent II, get sample behind the concentrate drying; Continue to separate the sample that obtains with preparative liquid chromatography: the separation condition of preparative hplc: chromatographic column is a Chinese nation semi-preparative column: Lichrospher C18; 10.0mm * 250mm, 5 μ m, mobile phase A is a water, and B is an acetonitrile, and the gradient elution program is as follows: in the time of 0 minute, mobile phase A is that 90% aqueous solution, Mobile phase B are 10% acetonitrile solution; In the time of 8 minutes, mobile phase A is that 81% aqueous solution, Mobile phase B are 19% acetonitrile solution; In the time of 60 minutes, mobile phase A is that 65% aqueous solution, Mobile phase B are 35% acetonitrile solution; Flow velocity is 3ml/min, and column temperature is a room temperature, and sample 100% dissolve with ethanol separates through preparative liquid chromatography, collects solution at time period 7.7～10.7min, and solution obtains active component behind concentrate drying.
2. the described Chinese medicine composition of claim 1 is characterized in that, the percentage by weight of each component is:
Radix Salviae Miltiorrhizae extract 31%～39%;
Cortex Moutan extract 61%～69%.
3. the described Chinese medicine composition of claim 1 is characterized in that, the percentage by weight of each component is:
Radix Salviae Miltiorrhizae extract 32%～38%;
Cortex Moutan extract 62%～68%.
4. the described Chinese medicine composition of claim 1 is characterized in that, the percentage by weight of each component is:
Radix Salviae Miltiorrhizae extract 33%～37%;
Cortex Moutan extract 63%～67%.
5. the described Chinese medicine composition of the arbitrary claim of claim 1-4 is characterized in that, the content of alkannic acid is 3～4% in the Radix Salviae Miltiorrhizae extract, and the content of salvianolic acid B is 92～94%, and the content of salvianolic acid E is 1～2%; The content of paeonol glycoside is 20～30% in the Cortex Moutan extract, and the content of paeonoside b is 35～45%.
6. contain the pharmaceutical formulation of the described Chinese medicine composition of the arbitrary claim of claim 1-4, it is characterized in that, make arbitrary pharmaceutical formulation that pharmaceutics is accepted according to the preparation method that pharmaceutics allows.
7. the described Chinese medicine composition of the arbitrary claim of claim 1-4 has application in the anti-myocardial ischemia drugs with function in preparation.
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| CN1981817A CN1981817A (en) | 2007-06-20 |
| CN1981817B true CN1981817B (en) | 2011-01-12 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1399953A (en) * | 2001-08-06 | 2003-03-05 | 天津市化妆品科学技术研究所 | Cosmetic capable of resisting nicotine |
| CN1546162A (en) * | 2003-12-17 | 2004-11-17 | 张正生 | Shuangdan extracts and its injection for treating coronary disease and angina pectoris and preparation thereof |
| CN1736422A (en) * | 2005-08-01 | 2006-02-22 | 浙江大学 | Composition of effective components of traditional Chinese medicine for treating cardiovascular disease |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1399953A (en) * | 2001-08-06 | 2003-03-05 | 天津市化妆品科学技术研究所 | Cosmetic capable of resisting nicotine |
| CN1546162A (en) * | 2003-12-17 | 2004-11-17 | 张正生 | Shuangdan extracts and its injection for treating coronary disease and angina pectoris and preparation thereof |
| CN1736422A (en) * | 2005-08-01 | 2006-02-22 | 浙江大学 | Composition of effective components of traditional Chinese medicine for treating cardiovascular disease |
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