CN104027525A - Drug for treatment of ischemic heart disease, preparation method and application thereof - Google Patents
Drug for treatment of ischemic heart disease, preparation method and application thereof Download PDFInfo
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- CN104027525A CN104027525A CN201310069825.4A CN201310069825A CN104027525A CN 104027525 A CN104027525 A CN 104027525A CN 201310069825 A CN201310069825 A CN 201310069825A CN 104027525 A CN104027525 A CN 104027525A
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Abstract
The invention discloses a Chinese herbal prescription proportioning and making process. The drug is a compound preparation prepared from the following raw materials by weight: 43%-97% of Salvia miltiorrhiza, 1.5%-48% of panax notoginseng, and 1.5%-48% of borneol. The materials are subjected to heat extraction by ethanol or other suitable solvents, and the obtained extract is prepared into the compound preparation. The invention also discloses application of the traditional Chinese medicine in treatment of ischemic heart disease.
Description
Technical field
The present invention relates to medicine of a kind of prevention and treatment ischemic heart desease and preparation method thereof, espespecially a kind ofly take the capsule that Chinese herbal medicine makes through special process as the special extracting method of prepared using, commodity are called heart venation open capsule.
Background technology
Ischemic heart desease comprises coronary artery obstruction that atherosclerotic lesion causes or narrow.Myocardial infarction is common ischemic heart desease disease clinically, and along with the development of interventional therapeutic technique, the treatment of acute myocardial infarction has also marched toward a new developmental stage in recent years.By intervene operation as coronary artery bypass, percutaneous Effect of Coronary Angioplasty art, thrombolytic art etc., can again recover blood flow, to improve the oxygen supply of patient's blood supply of cardiac muscle, redemption is on the verge of downright bad cardiac muscle, improve rapidly patient's clinical symptoms and late result, thereby reduced the mortality rate of patients of acute myocardial infarction, saved clinically the life of many patients with myocardial infarctions, thereby obtained promoting widely.The discovery of clinical practice in recent years, after the capable support of some patients were is implanted, although coronary blood flow has obtained recovery, myocardial ischemia improves, and patient's clinical symptoms and prognosis do not have clear improvement, even aggravation.Myocardial ischemia reperfusion injury (myocardial ischemia reperfusion injury, MIRI) is to recover after blood flow at heart ischemia, the phenomenon that its cellular metabolism dysfunction and structural deterioration increase the weight of on the contrary.Therefore Drug therapy remains the main path of Cardiovarscular.According to WHO statistics, to the year two thousand twenty acute coronary obstructive disease, will be the main cause of death in the world, myocardial ischemia reperfusion injury will be a great clinical problem, this has caused countries in the world scholar's extensive concern and research.
Radix Salviae Miltiorrhizae applicating history in China's medical treatment is long, and effect is very wide.Traditional medicine is recorded, and Radix Salviae Miltiorrhizae is cold in nature, bitter in the mouth, and GUIXIN warp, pericardium channel, specially walk blood system.Radix Salviae Miltiorrhizae energy promoting blood circulation, merit is arrogated to oneself blood circulation promoting and blood stasis dispelling, therefore be commonly called as, " Radix Salviae Miltiorrhizae supports four things simply." conventional preparation has Radix Salviae Miltiorrhizae Tabellae, FUFANG DANSHEN PIAN, the Radix Salviae Miltiorrhizae heart relax sheet, Radix Salviae Miltiorrhizae Injection and FUFANG DANSHEN ZHUSHEYE.Modern medicine study and clinical practice show, Radix Salviae Miltiorrhizae has coronary artery dilator, increases coronary artery blood flow, decreased heart rate, improves the effect of myocardial ischemia, is usually used in treating coronary heart diseases and angina pectoris, uncomfortable in chest, cardio palmus.Myocardial infarction, myocarditis can be treated, acute symptom and ischaemic ECG change can be improved.
Radix Notoginseng is tuber and the rhizome of araliaceae ginseng plant Radix Notoginseng (Panaxnotoginseng (Burk.) F.H.Chen), has dissipating blood stasis hemostasis, the effect of subduing swelling and relieving pain.Large quantity research shows the effects such as Radix Notoginseng has hemopoietic, the antithrombotic of promotion, resists myocardial ischemia, immunomodulating.Active component Radix Notoginseng total arasaponins in Radix Notoginseng has effect widely at cardiovascular system, comprises and alleviates myocardial ischemia/reperfusion injury, inhibition vascular smooth muscle cell proliferation, inhibition thrombosis and atherosclerosis, protection vascular endothelial cell, arrhythmia and ischemia resisting shock etc.
Rhizoma Dioscoreae Nipponicae (Dioscoreanipponica Makino) is the rhizome of the perennial liana Dioscorea nipponica Mak. Ningpo Yam Rhizome of Dioscoreaceae Wild yam, and modern pharmacology research shows, Rhizoma Dioscoreae Nipponicae tool improves cardiovascular function, antitussive and antiasthmatic, the multiple pharmacological effect such as eliminate the phlegm.Yam total saponin can improve Nutritional myocardium blood flow amount, and protection ischemic myocardium, prevents and treats arteriosclerosis, wherein best with Rhizoma Dioscoreae Nipponicae water-solubility saponin activity.
The logical side of heart venation is the compound recipe being combined into by Radix Salviae Miltiorrhizae, Radix Notoginseng, Rhizoma Dioscoreae Nipponicae three taste medicines, and the indication after this combination and combination was reported not yet under study for action.
Summary of the invention
The object of the invention is to provide a kind of logical square compound preparation of heart venation that can treat efficiently and prevent ischemic heart desease.
Another object of the present invention is to provide the individual composition proportion of the logical side of this heart venation.
A further object of the present invention is to provide the method that said ratio is prepared medicine of the present invention.
The present invention is implemented by following scheme.
Medicine of the present invention, its formulation ratio is (in weight percentage):
Radix Salviae Miltiorrhizae 43%～97%
Radix Notoginseng 1.5%～48%
Rhizoma Dioscoreae Nipponicae 1.5%～48%
Medicine optimization formula proportioning of the present invention is (in weight percentage):
Radix Salviae Miltiorrhizae 58%～90%
Radix Notoginseng 2.5%～30%
Rhizoma Dioscoreae Nipponicae 2.5%～30%
Medicine optimization formula proportioning of the present invention is (in weight percentage):
Radix Salviae Miltiorrhizae 70.3%～85.1%
Radix Notoginseng 5.05%～18.4%
Rhizoma Dioscoreae Nipponicae 5.05%～18.4%
Medicine optimum formula proportioning of the present invention is (in weight percentage):
Radix Salviae Miltiorrhizae 77.89%
Radix Notoginseng 11.05%
Rhizoma Dioscoreae Nipponicae 11.05%
The production method of medicine of the present invention is mainly: Radix Salviae Miltiorrhizae, Radix Notoginseng, the Rhizoma Dioscoreae Nipponicae medical material of learning from else's experience and pulverizing, add ethanol, and heating extraction 2～4 times, filters, merging filtrate, and filtrate is concentrated or be further purified the preparation that the extract obtaining is made
The present invention has following advantage:
1, found a kind of Chinese medicine compound for the treatment of ischemic heart desease.
2, this invention medicine is outstanding in protection treatment myocardial ischemia reperfusion injury disease effects, is better than FUFANG DANSHEN PIAN.
Below by the elaboration to the logical animal experiment study of heart venation, illustrate that the present invention is at the beneficial effect of pharmacopedics field application
Experimental example 1: the impact on anesthetized rat myocardial ischemia, myocardial infarction and relevant blood parameters
Observe the logical impact on experimental myocardial ischemia and myocardial infarction of new venation, by the variation of biochemical indicator and myocardial infarct size, inquire into the pharmacological action of its treatment ischemic heart desease.
1. method
1.1 experiment grouping and administrations: 91 experimental rats are divided into sham operated rats (normal saline), MIR group (normal saline), positive controls (TONGXINLUO JIAONANG 300mg/kg), FUFANG DANSHEN PIAN (300mg/kg), the logical low dose group (100mg/kg) of heart venation, the logical middle dosage group (300mg/kg) of heart venation, the logical high dose group (900mg/kg) of heart venation at random, below respectively organize equal gastric infusion, administration capacity is 1mL/100g body weight, successive administration 7 days, once a day, 1h modeling after last administration.Above medicine all, after precision weighing, is configured to suspension with distilled water and uses.
1.2 experimental techniques: rat is with after 2% pentobarbital sodium (50mg/kg) intraperitoneal injection of anesthesia, dorsal position is fixed, connect Physiological Signal Acquiring System and record rat II lead electrocardiogram, cervical region medisection, row endotracheal intubation (diameter is 2mmPE conduit), connect respirator (tidal volume 70Ml/kg, respiratory quotient 1.5: 1, 70 times/min of frequency), in the left breast unhairing of rat, cut, expose rib, separated 3～5 Intercostal muscles are opened breast chamber, heart is fully exposed, open pericardium, pulmonary conus left border and left auricle lower edge 2mm sentence 5/0 atraumatic suture inserting needle through superficial layer of myocardium (the about 1mm of the degree of depth, width 1.5-2mm), slip-knot following coronary artery occlusion left anterior descending branch (raising as ischemia sign with the high point of ECG T wave or ST section), cause left chamber antetheca myocardial ischemia, heart is put back to thoracic cavity and closed rapidly.After ischemia 30min, open thoracic cavity, unclamp silk thread, then pour into.A sham operated rats inserting needle is through superficial layer of myocardium, not ligation.Pour into abdominal aortic blood 5mL after 6h again, be placed in coagulant pipe, 3000r/min, 4 ℃ of centrifugal 10min, get upper serum standby.Measure serum glutamic oxalacetic transaminase (AST), lactic acid dehydrogenase (LDH), superoxide dismutase (SOD);
After pouring into again 6h, open thoracic cavity, cut heart, cut off auricle and blood vessel, with ice-cold normal saline flushing, be totally placed on-20 ℃.After freezing 1h, take out, section, is placed in the blue dye liquor of nitro tetrazole and dyes, and measures the area of the Yu Fei infarcted region, infarcted region of every myocardium bilateral, calculates the percentage by weight that infarcted region accounts for ventricle.
It is F check that each group of experimental result is first carried out homogeneity of variance analysis.If variance neat (F < 0.05), matches T with SPSS13.0 statistical software and checks; If heterogeneity of variance (F > 0.05), carries out non parametric tests with SPSS13.0.
2. result
(1) impact on ischemia-reperfusion rat blood serum biochemical indicator, with ischemia-reperfusion group ratio, heart venation is logical can suppress active rising of LDH, AST that myocardial ischemia, myocardial infarction cause; Can improve the activity of SOD, in Table 1.1.
(2) impact on myocardial ischemia reperfusion in rats infarction size, with ischemia-reperfusion group ratio, heart venation is logical can obviously reduce infarcted region, in Table 1.2.
(3) impact on myocardial ischemia reperfusion in rats pathological tissue, with ischemia-reperfusion group ratio, the logical group of heart venation alleviates cardiac muscle fiber swelling, alleviates inflammatory cell infiltration, and cardiac cell nucleus is with respect to the big or small homogeneous of ischemia-reperfusion group, and distribution uniform, is shown in Fig. 6.
(4), on the apoptotic impact of myocardial ischemia reperfusion in rats, with ischemia-reperfusion group ratio, the logical group of heart venation all can reduce apoptosis of cardiac muscle index, in Table 1.3.
Conclusion: experimental results show that, the have clear improvement effect of Acute Myocardial Ischemia in Rats and infarction of the logical tool of heart venation, while suppressing myocardial damage, Serum LDH, AST's overflows, reduce the activity of Serum LDH, AST, improve the activity of SOD, reduce myocardial infarction area, alleviate the pathology damage that ischemia-reperfusion causes, reduce apoptosis of cardiac muscle index.
Table 1.1 heart venation logical on the impact of ischemia-reperfusion rat blood serum SOD, LDH, AST (
n=8)
With model group comparison,
#p < 0.05,
##p < 0.01
The logical impact on myocardial ischemia reperfusion in rats infarct size of table 1.2 heart venation
With model group comparison,
##p < 0.01,
###p < 0.001
Table 1.3 heart venation is logical on the apoptotic impact of myocardial ischemia reperfusion in rats
With model group comparison,
#p < 0.05,
##p < 0.01,
###p < 0.001
Experimental example 2: the impact on anesthetized rat cardiac function
1. method
1.1 experiment grouping and administrations: 91 experimental rats are divided into sham operated rats (normal saline), MIR group (normal saline), positive controls (TONGXINLUO JIAONANG 300mg/kg), FUFANG DANSHEN PIAN (300mg/kg), diltiazem hydrochloride (16.5mg/kg), the logical low dose group (100mg/kg) of heart venation, the logical middle dosage group (300mg/kg) of heart venation, the logical high dose group (900mg/kg) of heart venation at random, below respectively organize equal gastric infusion, administration capacity is 1mL/100g body weight, successive administration 7 days, once a day, 1h modeling after last administration.Above medicine all, after precision weighing, is configured to suspension with distilled water and uses.
1.2 modeling methods: myocardial ischemia-reperfusion model, with experimental example 1.
1.3 monitoring methods: insert in respectively the subcutaneous of rat extremity, monitor ECG and heart rate by surveying Electrocardiographic 4 electrodes; Separated left femoral artery, the polyethylene catheter that insertion external diameter is 1mm, monitoring arterial pressure; Separated right common carotid artery, inserts polyethylene tube (internal diameter 1.5mm) to ventricle, monitoring left ventricular systolic pressure and latter stage diastolic pressure, indoor maximum rate of change.Stablize 2min, utilize Biopac MP150 type multi-path physiology function monitoring instrument to detect These parameters.
1.4 monitoring time points: before ischemia, ischemia 5min, pour into 4h again
2. result
(1) the logical 900mg/kg of heart venation can significantly improve the arterial pressure reduction that myocardial ischemia reperfusion injury causes, in Table 2.1.
(2) the logical 900mg/kg of heart venation can significantly improve the intraventricular pressure reduction that myocardial ischemia reperfusion injury causes, in Table 2.2.
(3) the logical 900mg/kg of heart venation can significantly alleviate myocardial ischemia reperfusion injury and cause that indoor maximum rate of change reduces, in Table 2.3.
Conclusion: experiment showed, the have clear improvement cardiac function of myocardial ischemia-reperfusion rat of the logical tool of heart venation.
The logical impact that ischemia-reperfusion rat artery is pressed of table 2.1 heart venation
With model group comparison,
#p < 0.05,
##p < 0.01,
###p < 0.001
Table 2.2 heart venation is led to the impact intrinsic pressure on ischemia-reperfusion rat cardiac ventricular
With model group comparison,
#p < 0.05,
##p < 0.01,
###p < 0.001
The logical impact on the large rate of change of the indoor amount of ischemia-reperfusion rat of table 2.3 heart venation
With model group comparison,
#p < 0.05,
##p < 0.01
Accompanying drawing explanation
Fig. 1 is the logical impact on ischemia-reperfusion rat blood serum superoxide dismutase (SOD) content of heart venation.
Fig. 2 is the logical impact on ischemia-reperfusion rat blood serum lactic acid dehydrogenase (LDH) content of heart venation.
Fig. 3 is the logical impact on ischemia-reperfusion rat blood serum glutamic oxaloacetic transaminase, GOT enzyme (AST) content of heart venation.
Fig. 4 is the logical impact on myocardial ischemia reperfusion in rats infarction size of heart venation
Fig. 5 is that heart venation is logical to myocardial ischemia reperfusion in rats infarction size NBT coloration result
To be that heart venation is logical organize HE (* 400) staining examine result to myocardial ischemia reperfusion in rats to Fig. 6.
Fig. 7 is the logical impact that ischemia-reperfusion rat artery is pressed of heart venation.
Fig. 8 is the logical impact intrinsic pressure on ischemia-reperfusion rat cardiac ventricular of heart venation.
Fig. 9 is the logical impact on the indoor maximum rate of change of ischemia-reperfusion rat of heart venation.
The embodiment that enumerates preparation and drug effect aspect below further describes the present invention, and to not restriction of the present invention.
[embodiment mono-]
Take: Radix Salviae Miltiorrhizae 180g Radix Notoginseng 60g Rhizoma Dioscoreae Nipponicae 60g
By pulverizing medicinal materials, add 75% soak with ethanol 30min, 8 times of amounts that the amount that adds ethanol is medical material.Heating and refluxing extraction 2h, filter, 75% alcohol heating reflux that medicinal residues add 8 times of amounts extracts 1.5h, filters merging filtrate, and filtrate is concentrated in right amount, be drying to obtain, according to content in pharmacopeia, record method, recording tanshinone ⅡA content in extract is 0.1%, Determination of Content of Ginsenoside Rg_1 is 1.36%, and dioscin content is 1.18%.
[embodiment bis-]
Take: Radix Salviae Miltiorrhizae 156g Radix Notoginseng 22g Rhizoma Dioscoreae Nipponicae 22g
The extraction of medical material, with embodiment mono-, records method according to content in pharmacopeia, and recording tanshinone ⅡA content in extract is 0.27%, and Determination of Content of Ginsenoside Rg_1 is 3.16%, and dioscin content is 2.56%.
Claims (12)
1. treat a medicine for ischemic heart desease, it is characterized in that it is the medicament of being made by the raw material of following weight proportioning
Radix Salviae Miltiorrhizae 43%～97%
Radix Notoginseng 1.5%～48%
Rhizoma Dioscoreae Nipponicae 1.5%～48%
2. the medicine for the treatment of ischemic heart desease according to claim 1, is characterized in that the weight proportion of each crude drug is
Radix Salviae Miltiorrhizae 58%～90%
Radix Notoginseng 2.5%～30%
Rhizoma Dioscoreae Nipponicae 2.5%～30%
3. the medicine for the treatment of ischemic heart desease according to claim 1, is characterized in that the weight proportion of each crude drug is
Radix Salviae Miltiorrhizae 70.3%～85.1%
Radix Notoginseng 5.05%～18.4%
Rhizoma Dioscoreae Nipponicae 5.05%～18.4%
4. the medicine for the treatment of ischemic heart desease according to claim 1, is characterized in that the weight proportion of each crude drug is
Radix Salviae Miltiorrhizae 77.89%
Radix Notoginseng 11.05%
Rhizoma Dioscoreae Nipponicae 11.05%
5. the preparation method of the medicine of the treatment ischemic heart desease described in claim 1 to 4 any one, is characterized in that the method is:
Radix Salviae Miltiorrhizae, Radix Notoginseng, the Rhizoma Dioscoreae Nipponicae medical material of learning from else's experience and pulverizing, add ethanol, and heating extraction 2～4 times filters, merging filtrate, and filtrate is concentrated or is further purified the preparation that the extract obtaining is made.
6. the preparation method of the medicine for the treatment of ischemic heart desease according to claim 5, the temperature that it is characterized in that heating extraction is 60～100 ℃.
7. the preparation method of the medicine for the treatment of ischemic heart desease according to claim 5, the amount that it is characterized in that described ethanol is the volume of 3～9 times.
8. the preparation method of the medicine for the treatment of ischemic heart desease according to claim 5, its feature is 65%～90% in the concentration of described ethanol.
9. the preparation method of the medicine for the treatment of ischemic heart desease according to claim 5, is characterized in that described purification process can be the said separation and refining method of any Chemistry for Chinese Traditional Medicine.
10. the preparation method of the medicine for the treatment of ischemic heart desease according to claim 5, is characterized in that described preparation can be said dosage form on any pharmaceutics.
The preparation method of the medicine of 11. treatment ischemic heart desease according to claim 5, is characterized in that described preparation is capsule.
The 12. ischemic heart medicines that according to claim 5 prepared by method, is characterized in that described ischemic heart desease comprises: coronary heart disease, myocardial ischemia reperfusion injury, myocardial infarction, myocarditis and other heart diseases that caused by myocardial ischemia.
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| CN112656883A (en) * | 2020-12-21 | 2021-04-16 | 黑龙江儒泰科技发展有限责任公司 | Blood-activating traditional Chinese medicine composition and application thereof |
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Application publication date: 20140910 |