CN1515276A - Medicine for preventing restenosis after interventional therapy of coronary heart disease and/or curing coronary heart disease and its preparation method - Google Patents
Medicine for preventing restenosis after interventional therapy of coronary heart disease and/or curing coronary heart disease and its preparation method Download PDFInfo
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Abstract
The present invention relates to a Chinese medicine preparation for preventing restenosis after interventional therapy of coronary heart disease and/or curing coronary heart disease and angina pectoris. The Chinese medicine preparation is composed of 20-80 portions of ligusticum root extract and 80-20 portions of red peony root extract as active component, and can be made into the oral preparations of capsule, tablet and granules and injection. Said invention also provides its preparation method.
Description
Technical field
The invention belongs to a kind of Chinese medicine preparation and preparation method thereof, particularly relate to Chinese medicine preparation of prevention coronary heart disease restenosis after interventional therapy and treatment angina pectoris and preparation method thereof.
Background technology
It is a comparatively sophisticated medical skill that patients with coronary heart disease is implemented interventional therapy, and it comprises percutaneous tranluminal coronary angioplasty (PTCA) and Stent etc.Reach the existing increasing patients with coronary heart disease of China at present in the world and accepted interventional therapy.But coronary heart disease restenosis after interventional therapy (RS) is focus, the difficult point of world's preventing and treating cardiovascular disease research field, still lacks real effectively treatment, prophylactic agent at present in the world, and often patient need implement PTCA or support implantation once more.
Domestic more existing researchs aspect application Chinese herb on the prevention restenosis at the 'Xue Fu Zhu Yu ' preparation of clinical practice, are studied more ligustrazine, hirudin, emodin, tripterine, decoction for Resuscitation and BUYANG HUANWU TANG etc. in addition as.But these researchs are confined to some links of restenosis more, thicken etc. as smooth muscle cell proliferation, blood vessel sarcolemma, and mostly these researchs are to carry out on rabbit or rat balloon injury model, domesticly do not see that as yet carrying out Chinese medicine with the pig restenosis model suppresses the experimentation report that restenosis forms.
The Chinese medicine preparation of angina pectoris present domestic great majority except that injection belong to the Chinese medicinal tablet and the capsule preparations of three quasi drugss, mostly be the Chinese medicine crude extract greatly, it is less that effective site is used as medicine, belong to the Chinese medicine preparation of two quasi drugss as the treatment that is used for coronary heart disease with Radix Puerariae total flavones, especially the Chinese medicine preparation formed of the above effective ingredient in Chinese of two flavors seldom.
Summary of the invention
The objective of the invention is to develop and a kind ofly can effectively prevent the Chinese medicine preparation of coronary heart disease restenosis after interventional therapy, this Chinese medicine preparation is again effectively to treat treating coronary heart disease and angina pectoris simultaneously.
Another purpose of the present invention provides and is used for effectively preventing coronary heart disease restenosis after interventional therapy medicine and the extraction process of treatment angina pectoris medicine active ingredient and the preparation method of medicine.
The Chinese medicine Rhizoma Chuanxiong is the dry rhizome of umbellate form plant Rhizoma Chuanxiong (Liqusticum Cnuanxioq Hort).The traditional Chinese medical science thinks that the hot temperature of Rhizoma Chuanxiong is nontoxic, is gas medicine in the blood, has blood circulation promoting regulates qi, an effect of the pain relieving that activates yang.Chinese medicine Radix Paeoniae Rubra is the dry rhizome of buttercup tannin plant Radix Paeoniae (Paeonca Lactifiora Pall), and Radix Paeoniae Rubra is bitter flat nontoxic, the merit of having blood dissipating blood stasis, mediation blood vessels.
Technical scheme of the present invention is to be that raw material adopts advanced process through extracting purification refine with Chinese medicine Rhizoma Chuanxiong, Radix Paeoniae Rubra,---Rhizoma Chuanxiong extract and the Radix Paeoniae Rubra total effective parts---Radix Paeoniae Rubra extract of preparing the Rhizoma Chuanxiong total effective parts respectively.With Rhizoma Chuanxiong extract and Radix Paeoniae Rubra extract is that effective ingredient preparation rationally can be used for preventing coronary heart disease restenosis after interventional therapy and/or treatment treating coronary heart disease and angina pectoris.
Particular content of the present invention is as follows:
One, the preparation of Rhizoma Chuanxiong extract:
1, extraction process
Get Rhizoma Chuanxiong coarse powder (crossing 20 mesh sieves), with 16 times of amount 80% alcohol reflux secondaries, each 1.5 hours, filter, merging filtrate reclaims ethanol, is concentrated into every milliliter and contains crude drug 0.5g, ethyl acetate extraction, the gained extract is with 2% sodium hydroxide extraction, and extract transfers to acidity with hydrochloric acid, and filtrate is passed through macroporous resin column, water eluting macroporous resin chloride ion to the eluent is negative, uses 40% ethanol elution.Reclaim ethanol, vacuum drying promptly gets Rhizoma Chuanxiong extract.(technological process as shown in Figure 1)
2, character: Rhizoma Chuanxiong extract is brown amorphous powder, and gas is special, mildly bitter flavor, be soluble in methanol, ethanol, ethyl acetate, aqueous alkali.
3, assay: mainly contain the ferulic acid that cardiovascular is had active function in the Rhizoma Chuanxiong extract, and contain a large amount of Rhizoma Chuanxiong phenolic acid.Show that after measured ferulic acid must not be less than 10.0% in the Rhizoma Chuanxiong extract, the Rhizoma Chuanxiong phenolic acid must not be less than 70.0%.
Two, the preparation of Radix Paeoniae Rubra extract:
1, extraction process:
Get Radix Paeoniae Rubra coarse powder (crossing 20 mesh sieves) with 16 times of amount 80% alcohol reflux secondaries, each 1.5 hours, filter, merging filtrate reclaims ethanol, be concentrated into every milliliter and contain crude drug 1g, put 0-4 ℃ of cold preservation 24 hours, filter, filtrate is passed through macroporous resin column, water flushing macroporous resin reducing sugar to the eluent is negative, and uses 30% ethanol elution.Recovery ethanol gets the thick cream of extract, and thick cream adds the ethyl acetate reflux, extract,, filters, and reclaims ethyl acetate, and vacuum drying gets Radix Paeoniae Rubra extract.(technological process as shown in Figure 2).
2, character: Radix Paeoniae Rubra extract is the amorphous powder of pale brown color, special, the bitter in the mouth of gas.Soluble in water, methanol, ethanol, ethyl acetate, insoluble in petroleum ether.
3, assay: Radix Paeoniae Rubra extract mainly contains has active function Radix Paeoniae general glycoside to the cardiovascular aspect, and contains a large amount of Radix Paeoniae Rubra phenolic acid.Show that after measured the Radix Paeoniae general glycoside must not be lower than 50.0% in the Radix Paeoniae Rubra extract, the Radix Paeoniae Rubra phenolic acid must not be less than 8.0%.
Three, the preparation of QIONGSHAO JIAONANG:
1, component (weight portion):
Rhizoma Chuanxiong extract 20-80 part
Radix Paeoniae Rubra extract 80-20 part
2, method for making: get Rhizoma Chuanxiong extract and Radix Paeoniae Rubra extract is ground into fine powder, mix with 85% alcoholic solution wet granulation, incapsulate promptly after the drying with oral adjuvant.
Of the present invention is also can add pharmaceutically acceptable carrier in the medicine of effective ingredient preparation with Rhizoma Chuanxiong extract and Radix Paeoniae Rubra extract, and described carrier comprises the conventional adjuvant that uses of pharmaceutical field.Also can be made into oral formulations and injections such as tablet, granule, oral liquid.
Four, results of pharmacodynamic test
1, QIONGSHAO JIAONANG test of pesticide effectiveness aspect the restenosis behind prevention coronary heart disease interventional therapy,
Adopt internationally recognized balloon expandable damage porcine coronary to cause the animal model of restenosis (RS) and Endothelin (FT) to cause and cultivate rabbit thoracic aorta smooth muscle cell (SMC) multiplicative model, systematic observation the drug effect of RS behind the QIONGSHAO JIAONANG prevention percutaneous coronary intervention.The result shows that QIONGSHAO JIAONANG can obviously suppress after the porcine coronary balloon injured intimal thickening and pathologic vessels and reinvent, reduces the tube chamber forfeiture, suppresses restenosis and form.
2, the test of pesticide effectiveness of QIONGSHAO JIAONANG aspect the treatment angina pectoris:
Adopt the healthy hybrid dog of ligation coronary artery, Wistar rat heart muscle ischemia model and Wistar rat myocardial ischemia and reperfusion damage model to carry out the test of pesticide effectiveness of QIONGSHAO JIAONANG.The result show QIONGSHAO JIAONANG have resist myocardial ischemia, anti peroxidation of lipid, minimizing myocardial cell enzyme spill to have and resist myocardial ischemia, antiplatelet aggregation and thrombosis, improve effects such as hemorheological property and certain protection heart contraction the planning function.
Five, toxicological test result:
, record maximum tolerated dose and be respectively 8g/kg body weight and 6g/kg body weight mice and rat oral gavage administration, one week of experimental observation with Cmax, maximum volume, be equivalent to 848 times and 636 times of clinical people's consumption; Percutaneous injection QIONGSHAO JIAONANG miscible fluid is down measured mice median lethal dose(LD 50) LD
50Be 1.84g/kg, be equivalent to 195 times of clinical consumption.
Give 24 weeks of rat continuous irrigation stomach to be equivalent to clinical or people's dosage 90 times, 30 times and 10 times respectively, do not find obvious toxic-side effects, 2 week of drug withdrawal the back observe and also do not find the retardance toxic reaction.Give Beaqla dog continuous irrigation 24 weeks of stomach to be equivalent to 50 times of clinical adult's consumption and 5 times respectively, 2 weeks of drug withdrawal observe and do not have obviously influence, and the main organs pathologic finding is not seen toxic reaction.
Result of the test shows that QIONGSHAO JIAONANG is the medicine of a safety non-toxic.
Six, clinical observation test
1, to preventing the clinical observation of coronary heart disease restenosis after interventional therapy:
Select the patients with coronary heart disease of 82 routine percutaneous tranluminal coronary angioplasty (PTCA) or Stent success, be divided into routine of western medicine treatment group (matched group) 42 examples and Western medicine at random and add QIONGSHAO JIAONANG group 40 examples.The variation of 6 months angina pectoris of patient's postoperative recurrence blood stasis integration, exercise stress test, myocardium radioisotope scanning, coronarography etc. are carried out follow-up observation, the result is as follows: two groups have 34 people and check coronarography, add Chinese drug-treated group 14 people, wherein restenosis 5 people; Matched group 20 people, restenosis 15 people wherein, two groups of contrasts have notable difference.Add Chinese drug-treated group angina pectoris relapse rate and acute myocardial infarction incidence rate and also significantly be lower than matched group.Do not find obvious toxic-side effects in the clinical application process.
2, the Preliminary Clinical Observation of QIONGSHAO JIAONANG treatment angina pectoris
Select angina pectoris patient 60 examples, be divided into two groups at random, QIONGSHAO JIAONANG group 30 examples wherein, male 16 examples, women 14 examples, 61.90 ± 8.68 years old age, the course of disease 5.67 ± 5.95 years; 30 examples are organized in the routine of western medicine treatment, male 11 examples, women 19 examples, 61.41 ± 6.75 years old age, the course of disease 6.24 ± 5.74 years.Two groups of patients' ordinary circumstance is similar substantially, has comparability.Observed result is as follows: A, curative effect to treat angina pectoris QIONGSHAO JIAONANG group, routine of western medicine treatment are organized clinical angina pectoris total effective rate and are respectively 90.00% and 76.67%, two groups relatively have notable difference (P＜0.05), subjective symptoms and blood stasis signs such as lip is dark, tongue with ecchymosis, hesitant pulse such as that QIONGSHAO JIAONANG can obviously be improved is uncomfortable in chest, cardiopalmus.B, ECG curative effect QIONGSHAO JIAONANG group, routine of western medicine treatment group total effective rate are respectively that there were significant differences between 66.67% and 40.00%, two group (P＜0.05).
Medicine QIONGSHAO JIAONANG of the present invention is carried out clinical observation, the group of taking medicine 3 administrations patient's every day, each 2, every 0.25g, take half a year continuously, can effectively prevent the generation of coronary heart disease restenosis after interventional therapy, and reduce the generation of angina pectoris recurrence and acute myocardial infarction incident.
It is that raw material is prepared effective ingredient in Chinese Rhizoma Chuanxiong extract and Radix Paeoniae Rubra extract through extracting purification refine with Chinese crude drug Rhizoma Chuanxiong, Radix Paeoniae Rubra that the present invention adopts advanced reasonably technology, and be that the active ingredient preparation is used to prevent the coronary heart disease restenosis after interventional therapy and treats angina pectoris that comparatively ideal zoopery result and clinical application effect are arranged with it.This medicine has no side effect, and comparatively clear and definite quality control standard is arranged, and is ideal Chinese medicine preparation.
China has capable PTCA of patients with coronary heart disease more than 20,000 and/or stenting present every year approximately, and existing more than 100 ten thousand patients of world wide accept the PTCA treatment.Medicine of the present invention can obviously reduce the generation of restenosis, has saved the expense of a large amount of costlinesses of implementing PTCA art and/or stenting once more for the patient.Having solved present prevention coronary heart disease restenosis after interventional therapy does not have the difficult problem of specific medicament.
Angina pectoris is the commonly encountered diseases frequently-occurring disease, and state this medicine of internal therapy II class Chinese medicine mostly is injection at present, and medicine of the present invention is component with effective site, and reliable curative effect is arranged, and taking convenience is for the angina pectoris patient provides a kind of good medicine.
Description of drawings:
Fig. 1 is a Rhizoma Chuanxiong extract extraction process flow chart.
Fig. 2 is a Radix Paeoniae Rubra extract extraction process flow chart.
Fig. 3 is a QIONGSHAO JIAONANG preparation technology flow chart.
The specific embodiment:
The preparation of embodiment 1 Rhizoma Chuanxiong extract
Get Rhizoma Chuanxiong and be processed as coarse powder (crossing 20 mesh sieves), take by weighing 50kg, add 800kg, concentration is 80% alcohol reflux secondary, each 1.5 hours, filtration discards medicinal residues, merging filtrate reclaims ethanol, is concentrated into every milliliter and contains crude drug 0.5g, and ethyl acetate extraction water liquid discards, extract is with 2% sodium hydroxide extraction, reclaim ethyl acetate, extract transfers to acidity with hydrochloric acid, and filtrate is by the D101 macroporous resin column, water eluting macroporous resin chloride ion to the eluent is negative, uses 40% ethanol elution.Reclaim ethanol with paste Rhizoma Chuanxiong extract vacuum drying.Get Rhizoma Chuanxiong extract 0.358kg, extract yield 0.716%.Measure by analysis that ferulaic acid content is 12.26% in the Rhizoma Chuanxiong extract, the Rhizoma Chuanxiong phenolic acid is 70.5%.
Embodiment 2: the preparation of Radix Paeoniae Rubra extract
Get Radix Paeoniae Rubra and be processed as coarse powder (crossing 20 mesh sieves), take by weighing 50kg, adding 800kg concentration is 80% alcohol reflux secondary, each 1.5 hours, filter and discard medicinal residues, merging filtrate reclaims ethanol, be concentrated into every milliliter and contain crude drug 1g, put 0-4 ℃ of following cold preservation 24 hours, filter and discard precipitate, filtrate is by the ZTC-1 macroporous resin column, water flushing macroporous resin reducing sugar to the eluent is negative, use 30% ethanol elution, reclaim ethanol and get the thick cream of extract, thick cream adds the ethyl acetate reflux, extract,, filter, reclaim ethyl acetate, vacuum drying gets Radix Paeoniae Rubra extract 1.55kg, extract yield 3.1%.Measure by analysis that content of paeoniflorin is 53.74% in the Radix Paeoniae Rubra extract.Radix Paeoniae Rubra phenolic acid 9.1%.
Embodiment 3: the preparation of QIONGSHAO JIAONANG
Get Rhizoma Chuanxiong extract 20g, Radix Paeoniae Rubra extract 80g is ground into fine powder and microcrystalline Cellulose 127g mixing sieves, and it is an amount of to spray into 85% ethanol, makes 1000 granules, and drying incapsulates promptly.
Embodiment 4: the preparation of QIONGSHAO JIAONANG
Get Rhizoma Chuanxiong extract 80g, Radix Paeoniae Rubra extract 20g is ground into fine powder and microcrystalline Cellulose 127g mixing sieves, and it is an amount of to spray into 85% ethanol, makes 1000 granules, and drying incapsulates promptly.
Embodiment 5: the preparation of QIONGSHAO JIAONANG
Get Rhizoma Chuanxiong extract 35g, Radix Paeoniae Rubra extract 75g is ground into fine powder and microcrystalline Cellulose 140g mixing sieves, and it is an amount of to spray into 85% ethanol, makes 1000 granules, and drying incapsulates promptly.
The experiment that embodiment 6, QIONGSHAO JIAONANG resistive connection are pricked coronary artery dog acute myocardial ischemia
Utilize ligation coronary artery method to cause healthy hybrid dog acute ischemia model, observe the drug effect that QIONGSHAO JIAONANG resists myocardial ischemia from the aspects such as change of myocardial ischemia scope, degree, myocardial infarction area and myocardium zymetology.Experimental data is shown in table 1,2,3,4:
Table 1 is respectively organized dog degree of myocardial ischemia (∑-ST, mv, X ± S)
Group 30min 60min 120min 180min
Blank group 5.48 ± 1.37
*2.48 ± 1.04
*▲ ▲ 1.48 ± 0.39
*▲ ▲ 0.96 ± 0.33
*△ △ ▲ ▲
Model group 8.71 ± 1.52 11.46 ± 4.13 14.86 ± 4.94 ▲ 17.34 ± 5.73 ▲
Sorbitrate group 8.83 ± 1.34 9.90 ± 3.14 11.54 ± 4.49 12.98 ± 3.45 ▲
The rhizome of chuanxiong Chinese herbaceous peony organizes 8.95 ± 2.20 9.03 ± 3.94 10.03 ± 3.54 9.24 ± 3.01 in a small amount
*
The a large amount of groups 8.91 ± 2.73 9.26 ± 3.23 7.66 ± 3.62 of rhizome of chuanxiong Chinese herbaceous peony
*8.36 ± 1.53
*△
Annotate: with compare * P＜0.05 with the time model, * * P＜0.01; With compare △ P＜0.05 with time sorbitrate group.Compare with self 30min, ▲ P＜0.05, ▲ ▲ P＜0.01.
Table 2 is respectively organized dog myocardial ischemia scope (N-ST, the number that leads, X ± S)
Group 30min 60min 120min 180min
Blank group 5.00 ± 1.41
*1.20 ± 0.45
*▲ ▲ 0.80 ± 0.4
5**▲ ▲ 0.60 ± 0.55
*▲ ▲
Model group 9.20 ± 2.59 9.80 ± 1.48 11.80 ± 2.39 12.60 ± 2.61
Sorbitrate group 9.20 ± 2.05 9.40 ± 2.97 10.60 ± 2.19 9.20 ± 1.30
*
Rhizome of chuanxiong Chinese herbaceous peony group 9.00 ± 2.55 9.40 ± 2.30 10.40 ± 1.67 9.00 ± 1.41
*
Rhizome of chuanxiong Chinese herbaceous peony big group 8.80 ± 2.17 9.20 ± 1.30 9.00 ± 1.22
*8.80 ± 1.30
*
Annotate: with compare * P＜0.05 with the time model group, * * P＜0.01; Compare with self 30min, ▲ P＜0.05, ▲ ▲ P＜0.01.
Table 3 is respectively organized the dog myocardial infarction area, and (quantitative tissue learn to be measured N-BT dyeing X ± S)
The group number of animals infarcted region/myocardium gross area (%)
Model group 5 13.51 ± 2.96
Sorbitrate group 5 8.43 ± 2.56
*
Rhizome of chuanxiong Chinese herbaceous peony group 5 7.25 ± 1.85
*
Big group 5 5.88 ± 2.51 of rhizome of chuanxiong Chinese herbaceous peony
*
Annotate: compare * P＜0.05, * * P＜0.01 with model group
Table 4 respectively organize the weight ratio that the dog infarcted myocardium accounts for whole heart (X ± S, %)
Group number of animals infarcted myocardium/whole heart
Model group 5 3.60 ± 1.01
Sorbitrate group 5 2.08 ± 0.61
*
Rhizome of chuanxiong Chinese herbaceous peony group 5 1.73 ± 0.36
*
Big group 5 1.57 ± 0.35 of rhizome of chuanxiong Chinese herbaceous peony
*
Annotate: compare * P＜0.05 with model group, * * P＜0.01
Conclusion: QIONGSHAO JIAONANG can obviously alleviate degree of myocardial ischemia, the scope of ligation coronary artery dog, dwindles the myocardial infarction area of the crown arteries and veins dog of ligation, reduces spilling of ligation coronary artery myocardium enzyme.And when resisting myocardial ischemia, do not increase the ischemic myocardium oxygen consumption.
Embodiment 7, QIONGSHAO JIAONANG are to the experiment of ligation coronary artery dog hemodynamic effects.
Shown in table 5,6
Table 5 is respectively organized acute ligation coronary artery dog coronary artery blood flow (L/min, the variation of X ± S)
Group basis 30min 60min 120min 180min
Blank group 0.46 ± 0.07 0.43 ± 0.16 0.40 ± 0.08 0.38 ± 0.07
*0.39 ± 0.08
*
Model group 0.44 ± 0.08 0.39 ± 0.09 0.31 ± 0.05 ▲ 0.28 ± 0.05 ▲ ▲ 0.22 ± 0.03 ▲ ▲
Sorbitrate group 0.49 ± 0.05 0.35 ± 0.07 ▲ ▲ 0.33 ± 0.06 ▲ ▲ 0.32 ± 0.06 ▲ ▲ 0.33 ± 0.05
*▲ ▲
Rhizome of chuanxiong Chinese herbaceous peony group 0.44 ± 0.03 0.35 ± 0.04 ▲ ▲ 0.32 ± 0.04 ▲ ▲ 0.30 ± 0.02 ▲ ▲ 0.30 ± 0.05
*▲ ▲
Rhizome of chuanxiong Chinese herbaceous peony big group 0.43 ± 0.04 0.33 ± 0.03 ▲ ▲ 0.30 ± 0.01 ▲ ▲ 0.30 ± 0.01 ▲ ▲ 0.32 ± 0.02
*▲ ▲
Annotate: with compare with the time model
*P＜0.05,
*P＜0.01; With own foundation value ratio, ▲ P＜0.05, ▲ ▲ P＜0.01.
Table 6 is respectively organized acute ligation coronary artery dog cardiac output (L/min, the variation of X ± S)
Group basis 30min 60min 120min 180min
Blank group 1.98 ± 0.43 1.78 ± 0.55 1.77 ± 0.46
*1.57 ± 0.46
*1.52 ± 0.44
*
Model group 1.68 ± 0.39 1.41 ± 0.38 1.14 ± 0.21 ▲ 1.00 ± 0.17 ▲ ▲ 0.78 ± 0.13 ▲ ▲
Sorbitrate group 1.76 ± 0.17 1.30 ± 0.23 ▲ ▲ 1.20 ± 0.19 ▲ ▲ 1.16 ± 0.18 ▲ ▲ 1.20 ± 0.15
*▲ ▲
Rhizome of chuanxiong Chinese herbaceous peony group 1.74 ± 0.14 1.34 ± 0.22 ▲ ▲ 1.21 ± 0.19 ▲ ▲ 1.10 ± 0.14 ▲ ▲ 1.14 ± 0.14
*▲ ▲
Rhizome of chuanxiong Chinese herbaceous peony big group 1.72 ± 0.13 1.28 ± 0.28 ▲ 1.18 ± 0.23 ▲ ▲ 1.18 ± 0.06 ▲ ▲ 1.22 ± 0.07
*▲ ▲
Annotate: and with time model group ratio
*P＜0.05,
*P＜0.01; With own foundation value ratio, ▲ P＜0.05, ▲ ▲ P＜0.01.
Conclusion: QIONGSHAO JIAONANG can increase ligation coronary artery blood flow coronarius and cardiac output, and the effect of certain protection ligation coronary artery dog heart contraction and diastolic function is arranged.
The experiment of embodiment 8, QIONGSHAO JIAONANG function of promoting blood circulation to disperse blood clots
Cause the stasis syndrome model of SD stress in rats with epinephrine, pass through hemorheology index, observe the influence of QIONGSHAO JIAONANG, observe the effect of QIONGSHAO JIAONANG rat experiment blood stasis model blood circulation promoting and blood stasis dispelling to indexs such as rat blood viscosity, platelet focusing platelet adhesion, cell aggregationes.Concrete experimental data is shown in table 7,8,9.
Table 7 Rhizoma Chuanxiong Radix Paeoniae Rubra extract different proportion is to the influence of rat blood viscosity (X ± S)
Blood viscosity (mpa.s)
Grouping number of animals 5S
-110S
-135S
-1120S
-1
Blank group 10 24.08 ± 2.83
*17.27 ± 1.75
*10.23 ± 1.09 6.49 ± 0.81
Model group 10 33.19 ± 4.68 22.83 ± 3.09 11.59 ± 1.84 7.32 ± 0.76
XUEFU ZHUYU JIAONANG group 10 29.22 ± 3.63 20.92 ± 2.38 12.02 ± 1.24 7.25 ± 0.60
QIONGSHAO JIAONANG small dose group 10 32.71 ± 5.84 22.66 ± 3.52 12.32 ± 1.62 7.62 ± 0.80
Dosage group 10 28.90 ± 2.35 in the QIONGSHAO JIAONANG
*21.77 ± 2.29 11.53 ± 1.02 7.04 ± 0.64
The heavy dose of group 9 23.03 ± 7.15 of QIONGSHAO JIAONANG
*16.07 ± 4.90
*9.01 ± 2.64
*5.43 ± 1.46
*
Annotate: compare * P＜0.05, * * P＜0.01 with model group
Table 8 QIONGSHAO JIAONANG to rat to the influence of erythrocyte rheology (X ± S)
Deformable index (%) erythrocyte aggregation index packed cell volume
Grouping number of animals 100S
-11500S
-1% % %
Blank group 10 17.20 ± 1.10
*31.83 ± 1.34
*35.39 ± 1.27
*17.45 ± 2.62
*41.35 ± 2.40
Model group 10 33.19 ± 4.68 22.83 ± 3.09 11.59 ± 1.84 22.82 ± 4.28 42.30 ± 3.64
XUEFU ZHUYU JIAONANG group 10 29.22 ± 3.63 20.92 ± 2.38 12.02 ± 1.24 20.90 ± 4.14 42.00 ± 1.73
QIONGSHAO JIAONANG small dose group 10 32.71 ± 5.84 22.66 ± 3.52 12.32 ± 1.62 21.51 ± 3.67 41.45 ± 2.73
Dosage group 10 28.90 ± 2.35 in the QIONGSHAO JIAONANG
*21.77 ± 2.29 11.53 ± 1.02 18.94 ± 2.60
*41.65 ± 2.04
The heavy dose of group 10 23.03 ± 7.15 of QIONGSHAO JIAONANG
*16.07 ± 4.90
*9.01 ± 2.64
*17.73 ± 2.32
*41.65 ± 2.05
Annotate: compare * P＜0.05, * * P＜0.01 with model group
The influence that table 9 Rhizoma Chuanxiong Radix Paeoniae Rubra extract different proportion focuses on platelet adhesion, platelet rat (X ± S)
The maximum collection rate of platelet adhesion rate platelet
Grouping number of animals % %
Blank group 10 32.20 ± 3.40
*52.07 ± 21.82
Model group 10 37.83 ± 6.06 70.39 ± 20.79
XUEFU ZHUYU JIAONANG group 9 36.17 ± 4.37 61.40 ± 14.87
QIONGSHAO JIAONANG small dose group 10 37.65 ± 3.32 55.40 ± 26.12
Dosage group 10 34.26 in the QIONGSHAO JIAONANG ± 4.27 49.19 ± 18.89
*
The heavy dose of group 10 30.85 ± 3.03 of QIONGSHAO JIAONANG
*52.27 ± 17.35
Annotate: compare * P＜0.05 with model group
Conclusion: QIONGSHAO JIAONANG can obviously reduce plasma concentration and the molecule number of rat platelet GMP-140, suppress ADP, collagen-induced rat platelet aggregation, reducing rat blood viscosity reduces the rat erythrocyte aggregation index, improves its deformability, reduce plasma fibrinogen content, suppress external thrombus and form.
Embodiment 9, QIONGSHAO JIAONANG are used to prevent the experiment of Chinese Small-sized pig percutaneous tranluminal coronary angioplasty (PTCA) back restenosis
Restenosis is a kind of transition reparation reaction behind the coronary artery local damage behind the percutaneous coronary intervention, to be balloon expandable cause platelet adhesion to the damage of blood vessel wall to its main cause, focusing also discharges multiple somatomedin, and then stimulate tunica media SMC to inner membrance migration and transition propagation, the a large amount of extracellular matrixs of justacrine (ECM), cause vascellum endometrial hyperplasia and pathologic vessels to reinvent, finally cause luminal stenosis.This experiment purpose be by coronary angiography ring pathomorphology inspection, SABC and put method such as inspection-free survey from luminal stenosis degree, pathologic vessels reinvent, the aspects such as propagation of intimal thickening, platelet activation SMC observe the drug action that restenosis forms after the anti-porcine coronary balloon injured of QIONGSHAO JIAONANG.Experimental data such as table 10,11,12,13,14,15,16,17.
Reach relevant rudimentary value in the art before each treated animal art of table 10
The low dose of rhizome of chuanxiong Chinese herbaceous peony of the logical group of matched group probucol group blood vessel rhizome of chuanxiong Chinese herbaceous peony heavy dose
Chinese Small-sized pig 76565
Death toll 21010
Body weight (kg) 32.4 ± 3.36 31 ± 2.74 31 ± 1.58 32 ± 3.32 30.4 ± 2.19
Coronarography
The sacculus tremulous pulse is than 1.40 ± 0.04 1.37 ± 0.10 1.42 ± 0.04 1.37 ± 0.09 1.42 ± 0.06
Coronary artery expansion 21.24 ± 0.06 22.24 ± 0.09 19.08 ± 0.04 24.99 ± 0.09 23.69 ± 0.05
(damage back) (%)
Histopathology
Pathological grading 2.6 ± 0.89 2.6 ± 0.89 2.6 ± 0.89 3 ± 0 2.4 ± 0.89
Damage integration 0.35 ± 0.18 0.31 ± 0.20 0.26 ± 0.10 0.31 ± 0.11 0.41 ± 0.20
Annotate: each is organized between the data credit by statistics and analyses there was no significant difference (P＜0.05).
Table 11 is respectively organized the morphological analysis result relatively
The low dose of rhizome of chuanxiong Chinese herbaceous peony of the logical group of matched group probucol group blood vessel rhizome of chuanxiong Chinese herbaceous peony heavy dose
Maximum inner film thickness (mm) 0.89 ± 0.40 0.54 ± 0.15 0.54 ± 0.18 0.48 ± 0.08 0.34 ± 0.05*
Official jargon area (mm
2) 0.90 ± 1.18 1.35 ± 0.83 1.35 ± 0.90 1.88 ± 0.91 2.01 ± 0.88 △
IEL is around area (mm
2) 2.20 ± 0.65 2.16 ± 0.64 2.00 ± 0.52 2.62 ± 1.03 2.52 ± 0.76
EEL is around area (mm
2) 3.22 ± 0.63 3.34 ± 0.62 3.12 ± 0.55 3.68 ± 1.18 3.40 ± 0.64
Media area (mm
2) 1.02 ± 0.11 1.18 ± 0.43 1.12 ± 0.43 1.06 ± 0.47 0.88 ± 0.30
New intima area (mm
2) 1.30 ± 0.68 0.81 ± 0.68 0.65 ± 0.50 0.74 ± 0.14 0.51 ± 0.27
Remaining tube chamber percentage ratio (%) 34 ± 37 62 ± 24 △ 64 ± 28 70 ± 7 △ △, 77 ± 14 △ △
Luminal stenosis percentage ratio (%) 66 ± 37 38 ± 24 △ 36 ± 28 30 ± 7 △ △, 23 ± 14 △ △
Proliferation index 0.43 ± 0.23 0.24 ± 0.18 △, 0.21 ± 0.15 △, 0.21 ± 0.04 △ △, 0.16 ± 0.09 △ △
RS damage index 1.14 ± 0.51 0.69 ± 0.26 0.69 ± 0.43 0.72 ± 0.14 0.37 ± 0.07*
Annotate: compare * P＜0.05 with matched group; Compare with matched group, △ P＜0.05, △ △ P＜0.01 is that covariant is carried out covariance analysis with the damage integration.
Table 12 is respectively organized coronarography result contrast
The low dose of rhizome of chuanxiong Chinese herbaceous peony of the logical group of matched group probucol group blood vessel rhizome of chuanxiong Chinese herbaceous peony heavy dose
Artery diameter (preceding, mm) 2.20 ± 0.33 2.05 ± 0.33 1.94 ± 0.12 2.22 ± 0.49 2.12 ± 0.34
Artery diameter (after, mm) 2.66 ± 0.34 2.49 ± 0.30 2.31 ± 0.08 2.75 ± 0.47 2.62 ± 0.45
Artery diameter (follows up a case by regular visits to mm) 1.34 ± 0.82 1.75 ± 0.47 1.63 ± 0.34 1.97 ± 0.51
*2.03 ± 0.30
Acute tube chamber obtains (mm) 0.43 ± 0.17 0.51 ± 0.10 0.47 ± 0.09 0.58 ± 0.03 0.55 ± 0.11
The later stage tube chamber is lost (mm) 1.32 ± 0.71 0.74 ± 0.39
*0.68 ± 0.28
*0.78 ± 0.33
*0.59 ± 0.28
*
Annotate: each is organized between the data credit by statistics and analyses there was no significant difference (P＜0.05).
Compare with matched group, * P＜0.05, * * P＜0.01, obtaining with acute tube chamber is that covariance is analyzed.
The influence of later stage tube chamber forfeiture due to each group of table 13 is reinvented neointimal hyperplasia and blood vessel
Heavy dose of each group of the low dose of rhizome of chuanxiong Chinese herbaceous peony of the logical group of matched group probucol group blood vessel rhizome of chuanxiong Chinese herbaceous peony is comprehensive
Acute tube chamber obtains (mm) 0.43 ± 0.17 0.51 ± 0.10 0.47 ± 0.09 0.58 ± 0.03 0.55 ± 0.11
The later stage tube chamber is lost (mm) 1.32 ± 0.71 0.74 ± 0.39
*0.68 ± 0.28
*0.78 ± 0.33
*0.59 ± 0.28
*
Average inner film thickness * 2 (mm) 0.71 ± 0.42 0.35 ± 0.29
*0.29 ± 0.24
*0.28 ± 0.03
*0.21 ± 0.12
*
Blood vessel is reinvented (mm) 0.60 ± 0.39 0.39 ± 0.22 0.39 ± 0.14 0.50 ± 0.31
*0.37 ± 0.23
*
Neointimal hyperplasia proportion (%) 51 ± 15 42 ± 19 35 ± 25 44 ± 27 35 ± 19 41 ± 20
Blood vessel is reinvented proportion (%) 49 ± 15 58 ± 19 65 ± 25 56 ± 27 65 ± 19 59 ± 20
Annotate: each is organized between the data credit by statistics and analyses there was no significant difference (P＜0.05).
Compare with matched group, * P＜0.05, * * P＜0.01, obtaining with acute tube chamber is that covariance is analyzed.
Respectively organized blood plasma GMP-140 content relatively in 3 days after the table 14 porcine coronary balloon injured
Group example number blood plasma GMP-140 content (mg/L)
Matched group 5 100.8 ± 12.35
Probucol group 5 94.14 ± 13.51
The logical group 5 76.20 ± 12.73 of blood vessel
Rhizome of chuanxiong Chinese herbaceous peony small dose group 5 77.62 ± 14.97
The heavy dose of group 5 66.14 ± 4.42 of rhizome of chuanxiong Chinese herbaceous peony
*▲
Annotate: * compares with matched group, P＜0.01, ▲ compare P＜0.05 with the probucol group
Table 15 is respectively organized the influence of medicine to the PCNA positive percentage
Group PCNA positive percentage (%)
Matched group 10.14 ± 3.50
Probucol group 7.46 ± 2.23%
The logical group 6.67 ± 2.91% of blood vessel
Rhizome of chuanxiong Chinese herbaceous peony small dose group 7.15 ± 2.50%
The heavy dose of group 4.87 ± 1.59% of rhizome of chuanxiong Chinese herbaceous peony
*
Annotate:
*Compare P＜0.01 with matched group
*, ▲ compare P＜0.05 with the probucol group
Table 16 is respectively organized comparison (the μ m of immunohistochemical staining collagen I type positive expression area
2)
Group collagen I type positive expression area
Matched group 8379.28 ± 2073.22
Probucol group 7706.98 ± 1934.07
The logical group 5765.24 ± 1627.87 of blood vessel
*
Rhizome of chuanxiong Chinese herbaceous peony small dose group 5989.49 ± 1533.97
The heavy dose of group 3949.45 ± 1204.76 of rhizome of chuanxiong Chinese herbaceous peony
*
Annotate:
*Compare * P＜0.05, * * P＜0.01 with matched group
Table 17 is respectively organized the influence of medicine to apoptotic cell positive expression area occupation ratio
Group apoptotic cell positive expression area occupation ratio (%)
Matched group 3.72 ± 2.09
Probucol group 4.52 ± 2.70%
The logical group 6.71 ± 3.09% of blood vessel
Rhizome of chuanxiong Chinese herbaceous peony small dose group 8.58 ± 3.84%
*
The heavy dose of group 10.43 ± 4.52% of rhizome of chuanxiong Chinese herbaceous peony
*
Annotate: compare * P＜0.05, * * P＜0.01 with matched group
Conclusion: QIONGSHAO JIAONANG has and suppresses behind the pig PTCA neointimal hyperplasia and pathologic vessels and reinvent, and reduces the tube chamber forfeiture, suppresses platelet activation, reduces the new intima collagen deposition, suppresses the SMC hypertrophy and induces the SMC apoptotic effect.
Claims (9)
1, a kind of prevention coronary heart disease restenosis after interventional therapy and/or treatment treating coronary heart disease and angina pectoris is characterized by the medicament that this drug main will be made up of Rhizoma Chuanxiong extract and Radix Paeoniae Rubra extract.
2, prevention coronary heart disease restenosis after interventional therapy according to claim 1 and/or treatment treating coronary heart disease and angina pectoris is characterized by described drug main and want the composition weight proportioning to be:
Rhizoma Chuanxiong extract 20-80 part Radix Paeoniae Rubra extract 80-20 part
3, prevention coronary heart disease restenosis after interventional therapy according to claim 1 and 2 and/or treatment treating coronary heart disease and angina pectoris, it is characterized by described medicine is QIONGSHAO JIAONANG, is made up of following component:
140 parts of 75 parts of microcrystalline Cellulose of 35 parts of Radix Paeoniae Rubra extracts of Rhizoma Chuanxiong extract
4, prevention coronary heart disease restenosis after interventional therapy according to claim 1 and 2 and/or treatment treating coronary heart disease and angina pectoris is characterized by described medicament and are the above dosage form of any pharmaceutics.
5, prevention coronary heart disease restenosis after interventional therapy according to claim 1 and/or treatment treating coronary heart disease and angina pectoris, the preparation method that it is characterized by described Rhizoma Chuanxiong extract is:
Get Rhizoma Chuanxiong coarse powder (crossing 20 mesh sieves), with 16 times of amount 80% alcohol reflux secondaries, each 1.5 hours, filter, merging filtrate reclaims ethanol, be concentrated into every milliliter and contain crude drug 0.5g, ethyl acetate extraction, the gained extract is with 2% sodium hydroxide extraction, extract transfers to acidity with hydrochloric acid, and filtrate is by macroporous resin column, and water eluting macroporous resin chloride ion to the eluent is negative, use 40% ethanol elution, reclaim ethanol, vacuum drying promptly gets Rhizoma Chuanxiong extract.
6, prevention coronary heart disease restenosis after interventional therapy according to claim 1 and/or treatment treating coronary heart disease and angina pectoris, the preparation method that it is characterized by described Radix Paeoniae Rubra extract is:
Get Radix Paeoniae Rubra coarse powder (crossing 20 mesh sieves) with 16 times of amount 80% alcohol reflux secondaries, each 1.5 hours, filter, merging filtrate reclaims ethanol, is concentrated into every milliliter and contains crude drug 1g, put 0-4 ℃ of cold preservation 24 hours, filter, filtrate is passed through macroporous resin column, water flushing macroporous resin reducing sugar to the eluent is negative, and use 30% ethanol elution, recovery ethanol, get the thick cream of extract, thick cream adds the ethyl acetate reflux, extract,, filters, reclaim ethyl acetate, vacuum drying gets Radix Paeoniae Rubra extract.
7, Rhizoma Chuanxiong extract according to claim 5, the main active and the content that it is characterized by Rhizoma Chuanxiong extract are: ferulic acid is no less than 10%, and the Rhizoma Chuanxiong phenolic acid is no less than 70%.
8, Radix Paeoniae Rubra extract according to claim 6, the main active and the content that it is characterized by Radix Paeoniae Rubra extract are: the Radix Paeoniae general glycoside is no less than 50%, and the Radix Paeoniae Rubra phenolic acid is no less than 8%.
9, the preparation method of preparation claim 3 described prevention coronary heart disease restenosis after interventional therapy and/or treatment treating coronary heart disease and angina pectoris QIONGSHAO JIAONANG is characterized by this medicine and is prepared by following method:
(1) preparation of Rhizoma Chuanxiong extract:
Get Rhizoma Chuanxiong coarse powder (crossing 20 mesh sieves), with 16 times of amount 80% alcohol reflux secondaries, each 1.5 hours, filter, merging filtrate reclaims ethanol, be concentrated into every milliliter and contain crude drug 0.5g, ethyl acetate extraction, the gained extract is with 2% sodium hydroxide extraction, extract transfers to acidity with hydrochloric acid, and filtrate is by macroporous resin column, and water eluting macroporous resin chloride ion to the eluent is negative, use 40% ethanol elution, reclaim ethanol, vacuum drying promptly gets Rhizoma Chuanxiong extract;
(2) preparation of Radix Paeoniae Rubra extract:
Get Radix Paeoniae Rubra coarse powder (crossing 20 mesh sieves) with 16 times of amount 80% alcohol reflux secondaries, each 1.5 hours, filter, merging filtrate reclaims ethanol, is concentrated into every milliliter and contains crude drug 1g, put 0-4 ℃ of cold preservation 24 hours, filter, filtrate is passed through macroporous resin column, water flushing macroporous resin reducing sugar to the eluent is negative, and use 30% ethanol elution, recovery ethanol, get the thick cream of extract, thick cream adds the ethyl acetate reflux, extract,, filters, reclaim ethyl acetate, vacuum drying gets Radix Paeoniae Rubra extract;
(3) preparation of QIONGSHAO JIAONANG:
Get Rhizoma Chuanxiong extract and Radix Paeoniae Rubra extract is ground into fine powder, mix with 85%7 alcoholic solution wet granulations, incapsulate promptly after the drying with an amount of oral adjuvant.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102940702A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN106039204A (en) * | 2016-06-06 | 2016-10-26 | 王嘉兴 | Traditional Chinese medicine composition for treating restenosis after coronary intervention and preparation method of traditional Chinese medicine composition |
-
2003
- 2003-01-08 CN CN 03100171 patent/CN1279941C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102940702A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN102940702B (en) * | 2012-10-31 | 2014-05-28 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN106039204A (en) * | 2016-06-06 | 2016-10-26 | 王嘉兴 | Traditional Chinese medicine composition for treating restenosis after coronary intervention and preparation method of traditional Chinese medicine composition |
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| Publication number | Publication date |
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| CN1279941C (en) | 2006-10-18 |
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