CN103800482B - A kind of pharmaceutical composition for the treatment of myocardial ischemia and its preparation method and application - Google Patents

A kind of pharmaceutical composition for the treatment of myocardial ischemia and its preparation method and application Download PDF

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CN103800482B
CN103800482B CN201410080318.5A CN201410080318A CN103800482B CN 103800482 B CN103800482 B CN 103800482B CN 201410080318 A CN201410080318 A CN 201410080318A CN 103800482 B CN103800482 B CN 103800482B
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pharmaceutical composition
preparation
radix
myocardial ischemia
treatment
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CN103800482A (en
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李兵晖
马学玉
徐辉
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Abstract

The invention belongs to field of medicaments, be specifically related to the pharmaceutical composition for the treatment of myocardial ischemia, particularly relate to a kind of Chinese medicine composition for the treatment of myocardial ischemia and preparation method thereof.Described pharmaceutical composition is prepared from by the Chinese crude drug of following weight portion: Radix Codonopsis 30-50, Semen Vaccariae 10-30, Radix Notoginseng 20-35, Semen Persicae 15-30, Radix Oenotherae erythrosepalae 15-35, Massa Medicata Fermentata 5-15.Pharmaceutical composition prescription of the present invention is simplified, safe and effective, preparation technology is simple, and have no side effect, patient compliance is higher, has extraordinary development and application prospect.

Description

A kind of pharmaceutical composition for the treatment of myocardial ischemia and its preparation method and application
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of pharmaceutical composition for the treatment of myocardial ischemia and its preparation method and application.
Background technology
Along with the change of social population's aging and human diet structure, the sickness rate of cardiovascular disease is in obvious ascendant trend in worldwide, and the health of the mankind in serious threat.Wherein ischemic heart desease is one of the most common clinical, cardiovascular disease that hazardness is maximum, and clinical main manifestations is the myocardial ischemia such as angina pectoris, myocardial infarction symptom.Along with the development of modern medicine, myocardial ischemia in prevention, diagnosis, all achieve development at full speed in treatment, but due to the many and machine-processed complexity of its complication, adds the limitation of medicine, for preventing and controlling bring certain difficulty.The medicines such as nitrate esters, calcium channel blocker, beta-blockers are Be very effective on treatment myocardial ischemia, important effect is had with the quality of life of improving patient to the life extending patient, but also there is limitation in these medicines, such as easily there is toleration in nitrate esters medicine, calcium channel blocker reflexive can cause sympathetic activation, and beta-blockers has harmful effect to blood fat, blood glucose.Therefore, an important research topic is still to the research of the exploration of medicaments for resisting myocardial ischemia and the mechanism of resisting myocardial ischemia.
Chinese medicine thinks that primary disease belongs to " thoracic obstruction ", " pained " category, and the sick position of primary disease is based on heart kidney, and basic pathogenesis is deficiency in origin and excess in superficiality, deficiency in origin based on internal organs virtual loss, the deficiency of YIN of can holding concurrently; Mark is real common with blood stasis stagnation of phlegm.As mentioned above, the chemicals for the treatment of primary disease has certain curative effect at present, but side effect is large; And often prescription is huge to treat the TCM Recipe medicine of primary disease, dosage form falls behind, and quality controllability is poor, and overall curative effect is poor, inconvenient patient's use.
Summary of the invention
The invention solves the problems referred to above that prior art exists, provide a kind of prescription and simplify, treat ischemic pharmaceutical composition safely and effectively.The present invention, from the rule for the treatment of of Chinese traditional treatment myocardial ischemia, through development test, by Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine, through processing, extracts, makes a kind of pharmaceutical composition for the treatment of myocardial ischemia.
According to an aspect of the present invention, provide a kind of compositions for the treatment of myocardial ischemia, it is formed by the Chinese drug preparation of following weight portion: Radix Codonopsis 30-50, Semen Vaccariae 10-30, Radix Notoginseng 20-35, Semen Persicae 15-30, Radix Oenotherae erythrosepalae 15-35, Massa Medicata Fermentata 5-15.
In a preferred embodiment, described Chinese medicine composition is preferably formed by the Chinese drug preparation of following weight portion: Radix Codonopsis 40, Semen Vaccariae 20, Radix Notoginseng 25, Semen Persicae 20, Radix Oenotherae erythrosepalae 25, Massa Medicata Fermentata 10.
According to a further aspect in the invention, provide the preparation method of described pharmaceutical composition, concrete steps are as follows: take Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine according to above-mentioned prescription proportioning, add the water of 8-15 times amount wherein, decoct three times, each 1-3 hour, collecting decoction, filter, filtrate is condensed into the clear paste (80 DEG C) that relative density is 1.05-1.15, add ethanol to alcohol content 60-80% (v/v), stir, leave standstill 12-24 hour, filter, decompression filtrate recycling ethanol, to obtain final product.
Further preferably, the preparation method of described pharmaceutical composition is specific as follows: take Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine according to above-mentioned prescription proportioning, add the water of 12 times amount wherein, decoct three times, each 2 hours, collecting decoction, filter, filtrate is condensed into the clear paste (80 DEG C) that relative density is 1.05-1.15, adds ethanol to alcohol content 70% (v/v), stirs, leave standstill 18 hours, filter, decompression filtrate recycling ethanol, to obtain final product.
In a preferred embodiment, according to the preparation method of this area routine, by adding suitable adjuvant, the present composition can be made oral formulations, the preparations such as such as granule, tablet, capsule, pill, powder, drop pill.
In accordance with a further aspect of the present invention, the purposes of described pharmaceutical composition in treatment myocardial ischemia is additionally provided.
Advantage of the present invention is:
Pharmaceutical composition prescription of the present invention is simplified, safe and effective, preparation technology is simple, and have no side effect, patient compliance is higher, has extraordinary development and application prospect.Result of the test of the present invention shows: adopt medicine composite for curing myocardial ischemia Be very effective of the present invention, and described pharmaceutical composition significantly can reduce the myocardial infarction area of cerebral ischemic rats, effectively improve the oxidation resistance of ischemic myocardium.Fully demonstrate the action character of Chinese prescription multicomponent, multipath, Mutiple Targets, for the progress of Chinese medicine in curing myocardial ischemia serves positive impetus.
Detailed description of the invention
Technical scheme of the present invention is further described by following embodiment.It is pointed out that following explanation is only illustrating the technical scheme that application claims is protected, any restriction not to these technical schemes.The content that protection scope of the present invention is recorded with appended claims is as the criterion.
embodiment 1
Prescription: Radix Codonopsis 30g Semen Vaccariae 15g Radix Notoginseng 35g
Semen Persicae 15g Radix Oenotherae erythrosepalae 20g Massa Medicata Fermentata 15g
Method for making: take Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine according to above-mentioned prescription proportioning, add the water of 8 times amount wherein, decocts three times, each 1.5 hours, collecting decoction, filter, filtrate is condensed into the clear paste (80 DEG C) that relative density is 1.05-1.15, add ethanol to alcohol content 60% (v/v), stir, leave standstill 12 hours, filter, decompression filtrate recycling ethanol, to obtain final product.
embodiment 2
Prescription: Radix Codonopsis 50g Semen Vaccariae 20g Radix Notoginseng 20g
Semen Persicae 30g Radix Oenotherae erythrosepalae 30g Massa Medicata Fermentata 5g.
Method for making: take Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine according to above-mentioned prescription proportioning, add the water of 15 times amount wherein, decocts three times, each 2.5 hours, collecting decoction, filter, filtrate is condensed into the clear paste (80 DEG C) that relative density is 1.05-1.15, add ethanol to alcohol content 80% (v/v), stir, leave standstill 24 hours, filter, decompression filtrate recycling ethanol, to obtain final product.
embodiment 3
Prescription: Radix Codonopsis 40 Semen Vaccariae 20 Radix Notoginseng 25
Semen Persicae 20 Radix Oenotherae erythrosepalae 25 Massa Medicata Fermentata 10.
Method for making: take Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine according to above-mentioned prescription proportioning, add the water of 12 times amount wherein, decocts three times, each 2 hours, collecting decoction, filter, filtrate is condensed into the clear paste (80 DEG C) that relative density is 1.05-1.15, add ethanol to alcohol content 70% (v/v), stir, leave standstill 18 hours, filter, decompression filtrate recycling ethanol, to obtain final product.
the pharmacodynamics test of embodiment 4 medicine composite for curing myocardial ischemia of the present invention
1. test method: get healthy adult experimental dog (23.69 ± 7.35) kg, male and female dual-purpose, be divided into 6 groups at random, often organize 8: (1) sham operated rats, (2) model group, (3) positive drug control group (DIAOXINXUE KANG JIAONANG, 50.0mg/kg), pharmaceutical composition of the present invention (3.2g crude drug/kg) group prepared by (4) embodiment 1-3.Dog pentobarbital sodium (30.0 mg/kg) iv anaesthetizes, and back of the body position is fixed, and cuts skin of neck, tracheal intubation, connects electric pulmotor.In left side, the 4th intercostal executes thoracotomy, expose heart, cut off pericardium, be separated lower 1/3 intersection in left anterior descending coronary artery trunk, threading in order to ligation, to wet cloth absorption method mapping epicardial electrogram (EECG) with multiple spot, mapping point M, divide normal district (control point), infarct border district and infarction center.Art finishes, and stablizes 20min, record each point EECG.Except sham operated rats, all the other respectively organize following coronary artery occlusion, preparation experiment ami model.Be separated duodenal administration, record ligation at once, after administration 30,60,90,120,150,180,240,360min each point EECG, raise total amplitude (Σ-ST, mV) with ST section and represent degree of ischemia.After record 360min, from venous blood sampling, separation of serum, surveys CPK, LDH activity in serum with semi-automatic seralyzer.Serum LPO level and SOD, GSH-Px activity is measured according to kit method.Take off heart, cut off trunk root and atrium along coronary sulcus, be cut into 5 by cross-section for equal for left ventricle Uniform, be placed in NBT dye liquor, dye 15min in 37 DEG C of constant water bath box.Infarcted region is not painted, and non-infarcted region is blueness by NBT dye.Myocardial infarction area is measured with medical image analysis system.
2, result of the test
2. 1 impact on dog with acute myocardial infarction myocardial infarction area and serum CPK, LDH activity: result of the test shows, model group animal comparatively sham operated rats myocardial infarction area, CPK, LDH activity obviously raises, and tool is very significant (P < 0. 01), show modeling success.The result that NBT staining observes myocardial ischemia infarct size shows, pharmaceutical composition group prepared by embodiment of the present invention 1-3 and the animal cardiac muscle infarct size of positive controls are starkly lower than model group (P < 0. 01).Biochemical test result shows that pharmaceutical composition group prepared by embodiment of the present invention 1-3 and positive controls compare with model group obviously can reduce serum CPK, LDH activity (P < 0. 05,0.01), and result of the test is in table 1.
Table 1
Group Myocardial infarction area (%) CPK (U/L) LDH (U/L)
Sham operated rats 9.9±1.4 ** 678.9±178.6 ** 127.7±38.6 **
Model group 31.8±1.9 1996.2±349.6 261.1±49.6
Positive controls 14.4±2.2 ** 1006.5±297.3 ** 148.2±28.5 **
Embodiment 1 13.8±1.2 ** 975.5±199.7 ** 159.8±24.5 **
Embodiment 2 13.4±2.5 ** 918.4±209.3 ** 153.6±19.4 **
Embodiment 3 12.3±1.6 ** 877.5±147.2 ** 146.2±20.1 **
Compare with model group: *p < 0.05, *p < 0.01
2. 2 impacts on dog with acute myocardial infarction serum LPO level and SOD, GSH-Px activity: pharmaceutical composition group prepared by embodiment of the present invention 1-3 and DIAOXINXUE KANG JIAONANG group and the obvious reduction serum LPO level of model group (P <0.01), improve SOD and GSH-Px activity (P < 0. 05,0. 01).Show that pharmaceutical composition of the present invention antagonism Acute Myocardial Ischemia may with the lipid peroxidation caused antioxidant radical, in reinforcement, activities of antioxidant enzymes is relevant, and result of the test is in table 2.
Table 2
Group LPO (nmol/L) SOD (nU/L) GSH-Px (nU/L)
Sham operated rats 9.4±1.4 ** 78.22±8.2 ** 288.4±55.6 **
Model group 23.8±1.3 36.4±6.9 138.1±41.6
Positive controls 15.4±2.7 ** 56.7±7.3 ** 278.2±36.2 **
Embodiment 1 14.8±2.1 ** 50.4±9.3 ** 259.8±27.9 **
Embodiment 2 14.4±2.3 ** 52.2±8.8 ** 263.6±19.5 **
Embodiment 3 13.9±1.9 ** 57.5±7.2 ** 276.3±22.4 **
Content of the present invention merely illustrates some claimed specific embodiments; one of them or more described technical characteristic can be combined with arbitrary one or more technical scheme in technical scheme; these technical schemes obtained through combination also in the application's protection domain, just as these technical schemes obtained through combination in the disclosure of invention concrete record.

Claims (4)

1. treat a pharmaceutical composition for myocardial ischemia, it is characterized in that, it is prepared from by the Chinese crude drug of following weight portion: Radix Codonopsis 40, Semen Vaccariae 20, Radix Notoginseng 25, Semen Persicae 20, Radix Oenotherae erythrosepalae 25, Massa Medicata Fermentata 10;
Wherein, the preparation method of described pharmaceutical composition is as follows:
Take Radix Codonopsis, Semen Vaccariae, Radix Notoginseng, Semen Persicae, Radix Oenotherae erythrosepalae, Massa Medicata Fermentata Six-element Chinese medicine according to compositions proportioning, add the water of 12 times amount wherein, decoct three times, each 2 hours, collecting decoction, filter, filtrate is condensed into the clear paste that relative density is 1.05-1.15 at 80 DEG C, add ethanol to alcohol content 70% (v/v), stir, leave standstill 18 hours, filter, decompression filtrate recycling ethanol, to obtain final product.
2. the pharmaceutical preparation containing pharmaceutical composition according to claim 1, is characterized in that, described pharmaceutical composition and pharmaceutically acceptable adjuvant are prepared into oral drug preparation.
3. pharmaceutical preparation according to claim 2, is characterized in that, described oral drug preparation is granule, tablet, capsule, pill, powder or drop pill.
4. the application of pharmaceutical composition according to claim 1 in the medicine of preparation treatment myocardial ischemia.
CN201410080318.5A 2014-03-06 2014-03-06 A kind of pharmaceutical composition for the treatment of myocardial ischemia and its preparation method and application Expired - Fee Related CN103800482B (en)

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WO2010043156A1 (en) * 2008-10-06 2010-04-22 天津天士力制药股份有限公司 Drop pill for treating coronary heart disease and preparation thereof
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CN1543999A (en) * 2003-11-19 2004-11-10 王保平 Chinese traditional medicine preparation for treating cardiac and cerebral vascular diseases and its preparation process
WO2010043156A1 (en) * 2008-10-06 2010-04-22 天津天士力制药股份有限公司 Drop pill for treating coronary heart disease and preparation thereof
TW201309314A (en) * 2011-08-22 2013-03-01 Tianjin Tasly Pharmaceutical Application of Salvia miltiorrhiza composition in preparing drug for secondary prevention of coronary heart disease

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