CN1176677C - Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents
Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process Download PDFInfo
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- CN1176677C CN1176677C CNB011183195A CN01118319A CN1176677C CN 1176677 C CN1176677 C CN 1176677C CN B011183195 A CNB011183195 A CN B011183195A CN 01118319 A CN01118319 A CN 01118319A CN 1176677 C CN1176677 C CN 1176677C
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- herba epimedii
- chinese medicine
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Abstract
The present invention relates to a Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process, particularly to an oral capsule which belongs to the technical field of the research and development of traditional Chinese medicines and new medicines, wherein effective components of traditional Chinese medicine epimedium is extracted by a modern technological means, and the present invention is also provided with a preparation of the effective components. The medicine is used for treating coronary heart diseases, and is superior to the famous medicine called as Diaoxinxuekang which belongs to the second category of domestic Chinese patent medicines on the aspect of treating myocardial ischemia.
Description
The present invention relates to a kind of Chinese medicine pharmaceutical composition for the treatment of coronary heart disease, relating in particular to the Herba Epimedii total flavones that is contained in the Chinese medicine Herba Epimedii is the Chinese medicine preparation of its effective ingredient, this medicine produces effect to the treatment of coronary heart disease, and the present invention also provides a kind of preparation method of this medicine.
Coronary heart disease is the disease of serious harm human health, and incidence and mortality rises year by year.According to the WHO report, the annual number 1,200 ten thousand of suffering from cardiovascular and cerebrovascular disease death in the whole world.Suffer from the coronary heart disease of hypertension number in the U.S.'s 200,000,000 populations and have 6,000 ten thousand.The annual new cases of China just have 1,150,000, and are annual dead up to 600,000, and the height of its sickness rate more than the death toll, is startling, is known as " human first killer ".In order to capture this disease, especially more outstanding aspect interventional therapy though western medicine and medical practitioners has been made achievement, but its side effect and relapse rate are difficult to solve, and China physician entrusts to the care of hope on the Chinese medicine for this reason.Though the medicine of traditional Chinese medical herbal treatment coronary heart disease constantly comes out at present, and shortcoming is in various degree always arranged, this is a major issue that troubles medical circle, also is to impel pharmaceutical industry to drop into financial resource and material resource incessantly, releases the main purpose of new drug.
Herba Epimedii is the dry aerial parts of Berberidaceae plant Epimedium Epimedium Brevicornum.Summer, autumn tap when stem, leafiness, remove thick stalk and impurity, dry or dry in the shade.Kind surplus global barrenwort has 40 mainly is distributed in the temperate zone and the subtropical zone in Asia, the Middle East, Europe.Homemade Herba Epimedii has 23 kinds and 4 mutation now, wherein has the distribution in the NORTHERN KOREA area except that Herba Epimedii E.koreanum, and all the other are China endemic species, are dispersed throughout all parts of the country, and are distributed more widely with the Yangtze river basin, wherein Sichuan
[3]And Guizhou
[4]Two provinces respectively are distributed with 13 kinds.Shennong's Herbal is classified them as middle product, and Li Shizhen (1518-1593 A.D.) claims it that effect of " beneficial vital essence, hard muscles and bones, benefit waist knee joint, heart tonifying power " is arranged in Compendium of Material Medica, and " it is certified products that Chinese pharmacopoeia version in 1985 has been collected these genus four kind of plant.
It is documented, contain 28 kinds of flavones ingredients in the Herba Epimedii, also have lignan component, ionone constituents, sesquiterpenoids composition, phenethanol glycosides composition etc. in addition.Wherein, flavones ingredient is the main component of treatment coronary heart disease, and Herba Epimedii total flavones is not a simple chemical compound, but comprises the flavonoid mixture of icariine, and its composition sees the following form.
Flavone compound in table 1 barrenwort
The sequence number compound name claims substituent group plant *
R
1R
2R
3Mp (℃) [α] °
DThe source document
l Baohuoside?VI Rham?
4?Rham Glc Me 240～245 da 29
wu 34
2 8-Prenylkaempferol- Rham?
4?xyl Glc Me 196～199 wu 34
4′-methylcther-3-
[xylosyl(1→4)
rhamnoside]-7-
glucoside
3 Epimedokoreanoside?I Rham?
3?Glc Glc Me 168 -105 ko 37
4
| |
6
Ac Ac
4 Sempervirenoside?A Rham?
3?xyl Glc Me 149～150 -99.6 se 31
4
| |
3
Ac Ac
5 Sempervirenosido?B Rham?
3?xyl Glc Me se 32
|
4
Ac
6 Baohuoside VII Rham?
4?Rham H Me da 29
7 2″-O- Rham?
2?Rham H Me 154～157 -72.4 ko 38
Rhamnosylicari-side
II
8 Epimedokoreanoside Rham?
2?xyl H Me 181 -44.5 ko 37
II |
4
Ac
9 Rcuhuoside Rham?
4?Glc Glc H 214～217 wu 34
pu 35
10 Baohuoide?V Rham?
4?Rham Glc H 195～199 da 28
11 Diphylloside?C Rham?
2?Glc Glc H 184～185 -76.3 di 15
|
2
Glc
12 Baohuoside?IV Rham Rham H da 28
13 Baohuoside?III Rham?
4?Rham H H 215～220 da 28
14 2″-O-Rhamnosyli- Rham?
2?Rham H H 172～177 -69.0 ko 38
karisoside?A
15 Baohusu 254～257 da 29
16 Quercitrin 179～180 ac 39
17 Kaemprerol-3-O-L- Rham H H 170～172 ac 39
rhamnoside
rhamnoside
18 Kaemprerol-3-O-L- Rham-Rham H H da 28
dirhamnoside
19 Sutchuenoside Rham?
4?Ac Rham H su 33
20 Kaempferol-3，7-O- Rham Rham H su 33
Ldirhamnoside
21 Sagittatin?A Rham?
2?xyl Rham H 183～185 -78.0 sa 36
3
22 Sagittatin?B Rham?
3?xyl Rham H 188～190 -37.0 sa 36
|
4
Ac
23 Acuminatin 151～152 ac 39
16 Tricin 270～274 da 29
* plant origin is by the first two letter representation of plant species name.
Put down in writing according to pharmacopeia, the extract of Herba Epimedii has kidney-replenishing, bone and muscle strengthening, the effect of wind-damp dispelling, not only hypertension, coronary heart disease, hyperlipidemia, infertility, neurasthenia and old functional disease etc. there are certain curative effect, also can be used for the treatment of chronic tracheitis, chronic hepatitis, poliomyelitis and hyperosteogeny etc.In traditional tcm therapy, can only be to take behind the decocting, this traditional method one is to be difficult at utmost bring into play drug effect, says from another point of view, the inconvenience of taking of Chinese medicine has been known.By drug efficacy study to effective ingredient in the Chinese medicine, and then realize extraction and utilization to this natural component, produce and on drug effect, be equal to even be better than synthetic drug, and on toxicity, be better than the pure Chinese medicinal preparation of synthetic drug, particularly pure Chinese medicine injection injection, this is the development to traditional medicine.
The object of the present invention is to provide a kind of Chinese medicine pharmaceutical composition for the treatment of coronary heart disease, effective ingredient wherein is the flavone compound from Herba Epimedii Chinese medicine, also claims Herba Epimedii extract.
Having the present invention further provides with described icariine extract is active component, is used for the treatment of the pure Chinese medicine pharmaceutical preparation and the related dose forms of coronary heart disease.
Another object of the present invention is to be provided for to treat the preparation method, particularly icariine preparation method of extract of this pure Chinese medicine medicine of coronary heart disease.
Pharmaceutical composition provided by the invention, it contains the ethanol extraction that obtains from the Herba Epimedii crude drug, the icariine extract that has comprised Herba Epimedii total flavones in the composition of this extract, main active wherein is a Herba Epimedii total flavones, from the pharmacodynamics angle, be used for the treatment of the pharmaceutical composition of coronary heart disease as the present invention, the content of the Herba Epimedii total flavones in the described Herba Epimedii extract preferably is not less than 55% more than 50%.
On this basis, the present invention has has also researched and proposed a kind of pure Chinese medicine pharmaceutical preparation for the treatment of coronary heart disease, and this Chinese medicine medicine is the effective active composition with above-mentioned Herba Epimedii extract, and has comprised acceptable auxiliary component on the pharmaceutics.
Pharmaceutical preparation of the present invention comprises injection and oral agents, wherein oral agents comprises capsule, oral liquid, tablet, granule etc., injection, particularly powder ampoule agent for injection then require the amount of Herba Epimedii total flavones in its effective ingredient to be not less than 80%, preferably are not less than 85%.
The present invention also provides a kind of preparation method of this pure Chinese medicine pharmaceutical preparation, and it comprises: be raw material with the Herba Epimedii, use ethanol extraction, and purified separation produces Herba Epimedii extract, the content that makes Herba Epimedii total flavones in this extract is more than 50%; With this Herba Epimedii extract is effective ingredient, is prepared into the pharmaceutical preparation of requirement according to practice of pharmacy.
The Herba Epimedii crude drug generally is to tap between summer, autumn, dries or the preservation of drying in the shade after removing thick stalk or impurity, should pulverize earlier before being used for extracting, and requires usually to pass through the 20-40 mesh sieve, and being beneficial to wherein, effective ingredient is fully extracted.Consider from the production angle, in the epimedium herb that the present invention selects for use, comprised that the general flavone content of above-mentioned various Herba Epimedii total flavones chemical compounds should be not less than 5%.
According to the embodiment of comparative optimization of the present invention, the method for extracting the icariine extract comprises that the following step poly-:
(1) the Herba Epimedii crude drug is pulverized back adding concentration at the ethanol extraction more than 70%;
This ethanol extract of concentrating under reduced pressure below (2) 60 ℃ reclaims ethanol;
(3) extracting solution after above-mentioned the concentrating is added in the D101 post, elder generation is washed till colourless with distilled water, and the ethanol elution eluent of reuse 50% is colourless;
(4) concentrating under reduced pressure below 45-50 ℃ reclaims ethanol to paste in the ethanol elution.
In the said extracted step, concentration of ethanol can not be less than 70%, consider from the angle that improves extraction ratio, concentration of ethanol is high more good more, from producing and the consideration of cost angle, the preferred ethanol of about 70% concentration that uses carries out the extraction of raw material, extracting method can be a percolation, reflux, or other feasible mode of operation, should keep bigger ratio between ethanol and the crude drug, complete with what guarantee to extract, about 8-10 alcoholic solution percolation or direct the backflow (if necessary doubly that can use raw material weight, can take repeatedly reflux, extract), the preferred percolation that adopts with the crude drug percolator of packing into, makes the ethanol submergence raw material of adding, transudate flows out from the bottom, constantly add solvent simultaneously and keep the submergence raw material, percolate is merged carry out concentrating under reduced pressure, low temperature helps extracting the stable of composition theoretically, but can increase the cost of production process, thus preferably 50-60 ℃ or more under the low temperature to the extracting solution concentrating under reduced pressure.In actual production, require to reclaim as much as possible ethanol, the concentration of concentrated solution is controlled to about 2 milliliters of medicinal liquids be equivalent to 1 gram crude drug amount, or control finishing of concentration process for 1.12-1.15 by measuring D20 ℃ of its relative density.
For helping the separation of effective ingredient, extracting solution after concentrating need be dispersed on the appropriate carriers, be to use polyamide in the technical scheme for example of the present invention but do not got rid of other feasible carrier mass, concentrated solution is disperseed by the polyamide granules that its 2-4 doubly measures, used ethanol elution then.The optimized technical scheme according to the present invention, with oven dry in advance, granularity is 60-120 purpose polyamide dress post, the specification and the material of used chromatographic column have no special requirements, can be selected according to demand of practical production, and operational approach filling routinely, but dress post amount should be no less than post high 2/3, the post of the ratio of preferably selecting diameter and post height for use in about 1: 6～1: 8 scope.Then concentrated medicament is added in the polyamide column, when using ethanol elution, elution speed is preferably about 850-1500ml/ branch and plants.
The eluent of collecting reclaims ethanol to flowing soaking paste at concentrating under reduced pressure below 60 ℃, preferred thickening temperature 50-60 ℃, this moment vacuum about 400-600Mpa, described flowing soaking paste, its 1 milliliter is equivalent to about 1-2 and restrains the crude drug amount.Through further solvent flashing, vacuum drying is pulverized, and can obtain described Herba Epimedii extract powder.
According to technical scheme of the present invention, this Chinese medicine preparation dosage form can be injection or oral formulations, and wherein oral formulations comprises capsule, oral liquid, tablet, granule etc.When the preparation oral formulations, the auxiliary type agent of selecting for use can be conventional fillers such as starch, dextrin or cyclodextrin, sucrose, stearate, preparation later stage preparation technology and equipment all belong to the routine techniques of pharmaceutical field, the present invention does not limit this, so will not describe in detail at this.
The preferred dosage form of the present invention is a capsule, and particularly hard capsule can be made injectable powder according to pharmacopedics conventional method refinement treatment extract.A preferred version as preparation method, preparation process further comprises after being condensed into the ethanol dilution of extractive of general flavone with 70-80% of paste and adds polyamide column, do not have icariine with 85-90% alcoholic solution gradient elution to eluent, eluent reclaims ethanol to there not being the alcohol flavor in concentrating under reduced pressure below 60 ℃; The concentrated solution that obtains is added in pretreated polyamide column, then with the ethanol more than 90% concentration once more gradient elution to eluent do not have icariine-II, eluent reclaims ethanol at concentrating under reduced pressure below 60 ℃, and the concentrate that obtains is handled according to a conventional method and added adjuvant and make hard capsule.
The used polyamide column of preparation method of the present invention can use the polyamide product filling of common specification to obtain, preferably use the granularity of polyamide to be the 60-120 order, specification and material to used chromatographic column also do not have specific (special) requirements, the size of post can be determined according to the actual treatment amount, but the chromatographic column of the ratio of preferably selecting diameter and post height for use in 1: 6～1: 8 scope, and dress post amount should be no more than post high 2/3.
Creativeness of the present invention is to have gone out Herba Epimedii extract by scientific and feasible method extraction separation from Herba Epimedii Chinese medicine, and further this extract is prepared into as effective ingredient and is used for the treatment of cardiovascular and cerebrovascular disease, particularly treat the Chinese medicine preparation of coronary heart disease.As previously described, the effective ingredient of medicine provided by the invention is the Herba Epimedii extract that comprises Herba Epimedii total flavones, for reaching goal of the invention, should be to the extraction ratio of Herba Epimedii total flavones in the crude drug more than 55%, the content of icariine also should be not less than 15% in this extract simultaneously.
For guaranteeing the quality of medicine, need in process of production the active constituent content in the final extract is detected at any time.The method that is used to detect described flavone compound can be by any feasible detection means and known method, and the present invention has proposed the feasible detection method of a cover at this.
At first, pass through efficient liquid phase chromatographic analysis, with the contrast of icariine standard substance spectrogram, proved that containing with the icariine is the epimedium flavone mixture (calculate the peak area of main component from spectrogram, icariine accounts for about 30%) of main component in extractive of general flavone.From ultra-violet absorption spectrum, can see, icariine standard substance and Herba Epimedii extract all have maximum absorption band at 270nm, so should think that Herba Epimedii extract is consistent substantially with the ultraviolet absorpting spectrum of icariine, the present invention has adopted ultraviolet-visible spectrophotometry standard curve to detect content of total flavone roughly in view of the above; Simultaneously, adopt the high performance liquid chromatogram external standard method, the icariine content by in standard curve detection and the control Herba Epimedii extract uses proof, the favorable reproducibility of testing result in actual production.Should be noted that this method only as one of quality control method of product of the present invention, should not get rid of other any method that meets the demands and operation.Particularly the extraction ratio assay of total flavones mixture is easy to realize for those skilled in the art, also can as above-mentioned be to indicate by contrast extract and raw material thing to obtain extraction ratio of effective constituents in the glycoside extract with the icariine at the light absorption value of 270nm, the effective dose that wherein contains icariine then can record by the HPLC external standard method.
Accompanying drawing 1 is the HPLC spectrogram of icariine standard substance.
Accompanying drawing 2 is HPLC spectrograms of the Herba Epimedii extract for preparing of the present invention.
The HPLC of icariine measures in the extract
The HPLC condition:
Mobile phase: methanol: water: acetic acid=60: 40: 0.3
Detect wavelength: 270nm
Flow velocity: 1ml/ minute
1, standard curve
Precision takes by weighing 105 ℃ of icariine reference substance 10.6mg that are dried to constant weight, and methanol solution also is settled to 10ml, in contrast product solution.Accurate reference substance solution 0.2,0.6,1.0,1.4, the 1.8ml of drawing, put respectively in the 10ml volumetric flask, methanol is diluted to scale, be mixed with concentration and be 0.0212,0.0636,0.1060,0.1484, the methanol solution of 0.1908mg/ml, respectively get 10ul and inject high performance liquid chromatograph, measure by above-mentioned chromatographic condition.Micrograms with the icariine reference substance is an abscissa, and peak area is the vertical coordinate mapping, the drawing standard curve.
Regression equation Y=2E+07X-6394.5
Range of linearity 0.212-1.908ug
Coefficient of determination r=0.9999
2, the mensuration of icariine in the Herba Epimedii extract
The preparation precision of reference substance solution takes by weighing the icariine reference substance 10mg that is dried to constant weight at 105 ℃, puts in the 10ml volumetric flask, adds dissolve with methanol and is settled to scale, shakes up, promptly.
The preparation precision of need testing solution takes by weighing the Herba Epimedii total flavones 10mg that is dried to constant weight at 80 ℃, puts in the 50ml measuring bottle, and dissolve with methanol also is settled to scale, shakes up, promptly.
The accurate need testing solution 10ul that draws of algoscopy injects high performance liquid chromatograph, measures, promptly.
This product is calculated by dry product and is contained icariine (C
33H
40O
15), must not be less than 15%.
For ease of understanding the present composition at the medical value aspect treatment and the prevention cardiovascular and cerebrovascular disease, the inventor uses the capsule medicament of the above method or embodiment and injection to finish the following pharmacology and the test of pesticide effectiveness:
One, acute toxicity test
Because of the toxicity of Herba Epimedii total flavones is extremely low, can not survey median lethal dose(LD 50), so represent its acute toxicity with maximum tolerated dose.Herba Epimedii total flavones is to Kunming mouse gastric infusion 3 times/day, Cmax 0.7g/ml, and maximum volume 0.4ml/10g body weight was observed seven days continuously, and animal does not have death, and maximum tolerated dose is the 84g/kg amount, is equivalent to clinical plan 8400 times with daily dose.
Two, long term toxicity test
● the oral Herba Epimedii total flavones long term toxicity test of rat
160 of healthy Wister rats, be divided at random matched group, Herba Epimedii total flavones little, in, big three dosage groups, 40 every group, male and female half and half are established one of matched group, three of administration groups.Irritate stomach with 100mg/kg, 300mg/kg, three kinds of dosage of 900mg/kg, matched group gives the equal-volume distilled water, every day 1 time, 6 times weekly, 26 weeks of successive administration.Three dosage treated animal ordinary circumstance, food ration, body weight change, urine analysis of blood, every hematology and blood parameters, organ weights, organ coefficients, system becomes celestial and histopathologic examination, relatively do not have significant difference with matched group, do not see the overt toxicity reaction.The convalescent period in 4 weeks after the drug withdrawal, observe every detection index and there is no slow toxicity.According to the result of above long term toxicity test, think that tentatively it is safe that rat " Herba Epimedii total flavones " 900mg/kg/d irritates stomach.
● the oral Herba Epimedii total flavones long term toxicity test of Beagle dog
Give the Beagle dog with Herba Epimedii total flavones three kinds of dosage 100mg/kg, 200mg/kg, 400mg/kg and irritate stomach, every day 1 time, 6 times weekly, successive administration 6 months.The general behavior activity of three dosage treated animals, food-intake, body weight gain, electrocardiogram detect, every hematology and blood parameters, urine analysis of blood, system become celestial, organ coefficient, histopathologic examination, with the relatively more equal not statistically significant of matched group, do not see the overt toxicity reaction.1 month convalescent period after the drug withdrawal, observe above all detection indexs and there is no slow toxicity.According to the result of long term toxicity test, tentatively think Beagle dog 400mg/kg oral be safe.
Three. pharmacodynamics test
1. Herba Epimedii total flavones influence that anesthetized dog is damaged due to the systemic heart acute myocardial ischemia
Originally studies show that: Herba Epimedii total flavones has significant protective effect to the experimental ischemic myocardium damage of dog.Infer that Herba Epimedii total flavones may be by stabilizing cell membrane to the protection mechanism of cardiac muscle, stop the membrane damage of ischemic myocardium, suppress peroxidating, increase free radical scavenging, increase myocardial metabolism etc. plays a role.The prompting Herba Epimedii total flavones may have potential clinical value for the treatment of ischemic heart desease.
(1) to the influence of dog myocardial ischemia (epicardial electrogram mapping)
● to dog degree of myocardial ischemia (the ST section is raised):
Three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group all have and obviously alleviate degree of myocardial ischemia (ST section) effect.Three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group all had the effect that reduces ST section level at after the administration 15 minutes after the administration 240 minutes except that 180 minutes, each time point is organized with NS relatively statistical significance (P＜0.05～P＜0.001); The effect of the heavy dose of group of Herba Epimedii total flavones 30,45,60 minutes time point reduction ST sections after administration all is better than the DIAOXINXUE KANG group, and statistical significance (P＜0.05) is arranged; In the Herba Epimedii total flavones, the effect that reduces the ST section of small dose group 45 minutes time points after administration all is better than the DIAOXINXUE KANG group, and statistical significance (P＜0.05) is arranged
● to influence in body dog myocardial ischemia scope (N-ST):
Three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group all have obvious minimizing myocardial ischemia scope (N-ST) effect.Three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group were all having the effect that reduces N-ST segment mark measuring point number in 240 minutes after the administration in 15 minutes after the administration, and each time point is organized with NS more all statistical significance (P
-＜0.05～P＜0.001); It is more obvious than DIAOXINXUE KANG group that the heavy dose of group of Herba Epimedii total flavones reduced myocardial ischemia scope (N-ST) effect at 15 minutes and 30 minutes, and statistical significance (P＜0.05) is arranged; The Herba Epimedii total flavones small dose group reduced myocardial ischemia scope (N-ST) effect at 60 minutes more obvious than DIAOXINXUE KANG group, and statistical significance (P＜0.05) is arranged.
(2) to the influence of infarction size due to body dog coronary ligation 5 hours:
Show myocardial infarct size with TTC dyeing.Three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group all have the effect of obviously dwindling myocardial infarct size, with the NS group significant difference (P＜0.05～P＜0.01) are arranged relatively.In the Herba Epimedii total flavones, heavy dose of group dwindles the effect of myocardial ischemia scope than DIAOXINXUE KANG group slightly obviously, but statistics does not have difference (P＞0.05).
(3) to the influence of sero-enzyme
● to influence at body dog myocardial ischemia CPK:
After coronary artery ligation 2 hours, CPK obviously raise, and increases gradually along with the prolongation of ligation time, with own control comparative statistics before the ligation significant difference (P＜0.01～P＜0.001) is arranged; Three dosage groups of Herba Epimedii total flavones had the effect of obvious reduction CPK in 2 and 5 hours after ligation, with the NS group of identical time point significant difference (P＜0.05～P＜0.01) is arranged relatively; DIAOXINXUE KANG also has the effect that reduces CPK, but does not relatively have statistical significance (P＞0.05) with the NS group.The heavy dose of effect that reduces CPK of Herba Epimedii total flavones is compared slightly variant with the DIAOXINXUE KANG group.
● to influence at body dog myocardial ischemia LDH:
In the Herba Epimedii total flavones, small dose group after ligation 2,4 hours, the heavy dose of group of Herba Epimedii total flavones all had the effect of obvious reduction LDH in 2,3 hours after ligation, with the NS group of identical time point significant difference (P＜0.05) is arranged relatively; And DIAOXINXUE KANG does not reduce the effect of LDH.In the Herba Epimedii total flavones, the effect that reduced LDH after ligation in 2 hours of heavy dose of group is better than with time point DIAOXINXUE KANG group (P＜0.05)
-
(4) to the influence of the catabolite-malonaldehyde (MDA) of lipid peroxide:
3 hours malonaldehyde begin to raise after ligation, after ligation, obviously raise in 4,5 hours, and before NS group and self ligation significant difference (P＜0.01) is arranged relatively, three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group all had the effect of tangible reduction malonaldehyde in 3,4,5 hours after ligation, the effect of 4 hours reduction malonaldehyde is better than the DIAOXINXUE KANG group after ligation; And significant difference (P＜0.01～0.001) is relatively arranged with the NS of identical time point group.
(5) to the influence of myocardial metabolism blood lactate level:
3 hours lactate levels begin to raise after ligation, after ligation, obviously raise in 4,5 hours, and before NS group and self ligation significant difference (P＜0.001) is arranged relatively, three dosage groups of Herba Epimedii total flavones and DIAOXINXUE KANG group after ligation 4 hours be the effect that the therapeutic administration all had tangible reduction lactic acid in 2 hours; And significant difference (P＜0.001) is relatively arranged with the NS of identical time point group.
(6) to the influence of superoxide dismutase (SOD):
3 hours SOD begin to descend after ligation, obviously descend in 6 hours after ligation, and before NS group and self ligation significant difference (P＜0.05) are arranged relatively, and three dosage groups of Herba Epimedii total flavones all had the effect of tangible increased SOD in 6 hours after ligation; And statistical significance (P＜0.05～0.01) relatively being arranged with the NS of identical time point group, the DIAOXINXUE KANG group all has the effect of tangible increased SOD in 6 hours after ligation.
2. Herba Epimedii total flavones is to the neural influence of mice:
Adopt wilderness method and rotating rods method to experimentize: get 80 of healthy Kunming mouses, male and female half and half are divided into four groups at random: normal control, Herba Epimedii total flavones be little, in, heavy dose of group, 20 every group.Herba Epimedii total yellow little, in, heavy dose of group gives 50mg/kg, 100mg/kg and 150mg/kg respectively, the normal control group gives the equivalent normal saline.Behind the gastric infusion 40 minutes, adopt the wilderness laboratory method, observe, write down mice and put into active lattice number in the case of wilderness.Mice extremity are gone in the same lattice and have just been walked lattice, and mean activity lattice number between comparative control group and administration group group is judged its significance with the t check.
The result shows Herba Epimedii total flavones movable and not influence of passive activity to the mice wilderness.
3. Herba Epimedii total flavones is to the influence of cardiovascular system and respiratory system:
Adopt the anesthetized dog method: laboratory animal is with pentobarbital sodium (30mg/kg) intravenous anesthesia.Lie on the back in laboratory table, separate the left side femoral artery, intubate connects pressure transducer, surveys arteriotony through amplifier.Place electrocardiogram limbs crosslinking electrode, lead electrocardiogram and calculate heart rate through ecg amplifier mapping II.All indexs all are recorded in RM-6000 type (production of Japanese photoelectricity company) and lead road physiology monitor more.Measure respiratory frequency and amplitude of respiration through amplifier.Execute abdominal operation, separate the duodenum stage casing, intubate is in order to giving institute's reagent thing.Operation finishes, after treating that all observation index are stable, value before the record medicine, feed institute's reagent thing through duodenum, and behind medicine, carried out record in 30,60,90,120,150,180,210,240 minutes, and every observation index data are carried out statistical procedures, carry out self comparison with before the measured values of different observing times and the administration, and compare between organizing, judge its significance with the t check.
Experimental result shows that Herba Epimedii total flavones has obvious reduction effect to anesthetized dog cardiovascular system blood pressure, and to heart rate and not influence of electrocardiogram; Herba Epimedii total flavones to respiratory system both respiratory frequency and amplitude of respiration all less than influence.
Pharmaceutical composition of the present invention has following outstanding feature:
1. high-efficiency low-toxicity
2. active ingredient is clear and definite, and is quality controllable
3. simple process is easy to industrialization
4. plant material is cheap and easy to get
5. indication is wide, and market capacity is big
Claims (8)
1, a kind of Chinese medicine composition for the treatment of coronary heart disease, it is to make solvent with concentration greater than 70% ethanol, adopts percolation, reflow method to extract the Herba Epimedii total flavones extract that obtains from the Herba Epimedii crude drug, this extract obtains by the following method:
(1) with the above ethanol extraction Herba Epimedii crude drug of 70% concentration;
This ethanol extract of concentrating under reduced pressure below (2) 60 ℃;
(3) extracting solution after above-mentioned the concentrating is passed through the D101 macroporous resin column, elder generation is washed till colourless with distilled water, and the ethanol elution of reuse 50% is collected ethanol elution to colourless;
(4) eluent is being evaporated to paste below 45-50 ℃.
2, the described Chinese medicine composition of claim 1, the content that it is characterized in that Herba Epimedii total flavones in this extract is more than 50%, and the content of icariine is more than 15%.
3, the described Chinese medicine composition of claim 1, the elution speed when it is characterized in that ethanol liquid eluting wherein is the 850-1500 ml/min.
4, a kind of Chinese medicine preparation for the treatment of coronary heart disease is characterized in that it is made by described compositions of claim 1 and pharmaceutics acceptable auxiliary.
5, the described Chinese medicine preparation of claim 4, its dosage form comprises injection and oral formulations.
6, the described Chinese medicine preparation of claim 5, its dosage form is an oral capsule, and the content of the Herba Epimedii total flavones in the described Herba Epimedii extract is more than 50%, the content of icariine is more than 15%.
7, the described Chinese medicine preparation of claim 5, its dosage form is a freeze-dried powder injection, and the content of the Herba Epimedii total flavones in the described Herba Epimedii extract is more than 80%.
8, the preparation method of the described Chinese medicine preparation of claim 7, it is characterized in that may further comprise the steps: with claim 1 is described after concentrating extracting solution with 70% ethanol dilution after in the adding D101 post, wash with water earlier to colourless, it is colourless that reuse 50% alcoholic solution is eluted to eluent, and eluent reclaims ethanol to there not being the alcohol flavor in concentrating under reduced pressure below 45-50 ℃; In the polyamide column of concentrated solution adding after giving processing that obtains, colourless with the ethanol elution more than 70% concentration to eluent, collect eluent and reclaim ethanol at concentrating under reduced pressure below 45-50 ℃, the concentrate that obtains is handled according to a conventional method and is added adjuvant and make freeze-dried powder injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011183195A CN1176677C (en) | 2001-05-23 | 2001-05-23 | Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process |
Applications Claiming Priority (1)
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| CNB011183195A CN1176677C (en) | 2001-05-23 | 2001-05-23 | Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process |
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| CN1386526A CN1386526A (en) | 2002-12-25 |
| CN1176677C true CN1176677C (en) | 2004-11-24 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101040889B (en) * | 2006-03-20 | 2010-10-27 | 周亚伟 | Traditional Chinese medicinal prepns. for treating osteoporosis |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101607976B (en) * | 2008-06-19 | 2013-09-04 | 贵州省中国科学院天然产物化学重点实验室 | Method for preparing icariin |
| CN103937655B (en) * | 2014-05-20 | 2015-07-15 | 劲牌有限公司 | White spirit with anti-fatigue function and production method thereof |
-
2001
- 2001-05-23 CN CNB011183195A patent/CN1176677C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101040889B (en) * | 2006-03-20 | 2010-10-27 | 周亚伟 | Traditional Chinese medicinal prepns. for treating osteoporosis |
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| Publication number | Publication date |
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| CN1386526A (en) | 2002-12-25 |
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