Summary of the invention
The object of the present invention is to provide and a kind ofly can effectively treat cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, arrhythmia, hyperlipidemia and Chinese medicine composition with low cost, that toxic and side effects is little and preparation method thereof.
The Chinese medicine composition of treatment coronary heart disease of the present invention, angina pectoris, arrhythmia, hyperlipidemia; make by following component: Moschus 5-20 weight portion; Calculus Bovis 12-50 weight portion; sodium cholate 60-250 weight portion, Venenum Bufonis 12-50 weight portion, Margarita 30-120 weight portion; Borneolum Syntheticum 40-160 weight portion; Radix Notoginseng 1500-15000 weight portion, Radix Ginseng 150-600 weight portion, Cornu Bubali dry extract 50-200 weight portion.
The Chinese medicine composition of cardiovascular and cerebrovascular diseases such as treatment coronary heart disease of the present invention, angina pectoris, arrhythmia, hyperlipidemia can be made the dosage form on any pharmaceutics, comprises pill, capsule, tablet, granule, soft capsule or powder.
The preparation method of the various common formulations of Chinese medicine composition of the present invention below is described respectively:
1, the preparation of pill: the 20-90% that gets the pseudo-ginseng amount extracts Radix Notoginseng total arasaponins; all the other Radix Notoginseng and Moschus, Calculus Bovis, sodium cholate, Venenum Bufonis, Margarita, Borneolum Syntheticum, Radix Ginseng, Cornu Bubali dry extract pulverize separately; again with the Radix Notoginseng total arasaponins facing-up; sieve; mixing; with the general ball of ethanol, Radix Glycyrrhizae charcoal coating, cold drying promptly.
2, the preparation of capsule: the 20-90% that gets the pseudo-ginseng amount extracts Radix Notoginseng total arasaponins; all the other Radix Notoginseng and Moschus, Calculus Bovis, sodium cholate, Venenum Bufonis, Margarita, Borneolum Syntheticum, Radix Ginseng, Cornu Bubali dry extract pulverize separately; again with the Radix Notoginseng total arasaponins facing-up; cold drying; sieve; mixing is filled, and makes capsule.
3, the preparation of tablet: the 20-90% that gets the pseudo-ginseng amount extracts Radix Notoginseng total arasaponins, and all the other Radix Notoginseng and Moschus, Calculus Bovis, sodium cholate, Venenum Bufonis, Margarita, Borneolum Syntheticum, Radix Ginseng, Cornu Bubali dry extract pulverize separately are again with the Radix Notoginseng total arasaponins facing-up; cold drying is sieved, mixing; granulate, be pressed into tablet.
4, the preparation of granule: the 20-90% that gets the pseudo-ginseng amount extracts Radix Notoginseng total arasaponins, and all the other Radix Notoginseng and Moschus, Calculus Bovis, sodium cholate, Venenum Bufonis, Margarita, Borneolum Syntheticum, Radix Ginseng, Cornu Bubali dry extract pulverize separately are again with the Radix Notoginseng total arasaponins facing-up; cold drying; sieve, mixing is made granule.
5, preparation of soft capsule: the 20-90% that gets the pseudo-ginseng amount extracts Radix Notoginseng total arasaponins; all the other Radix Notoginseng and Moschus, Calculus Bovis, sodium cholate, Venenum Bufonis, Margarita, Borneolum Syntheticum, Radix Ginseng, Cornu Bubali dry extract pulverize separately; again with the Radix Notoginseng total arasaponins facing-up; sieve; mixing; add an amount of Polyethylene Glycol-400 and a spot of glycerol, mixing is pressed into soft capsule.
6, the preparation of powder: the 20-90% that gets the pseudo-ginseng amount extracts Radix Notoginseng total arasaponins, and all the other Radix Notoginseng and Moschus, Calculus Bovis, sodium cholate, Venenum Bufonis, Margarita, Borneolum Syntheticum, Radix Ginseng, Cornu Bubali dry extract pulverize separately are again with the Radix Notoginseng total arasaponins facing-up; sieve; mixing, powder is made in cold drying.
Described Radix Notoginseng total arasaponins is to get Radix Notoginseng powder to be broken into coarse powder, uses the 30-90% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.0-6.5 with the 15%-30% hydrochloric acid solution, placement is spent the night, filter, filtrate is extracted with the ether jolting, discards ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol makes at 30-90 ℃ of vacuum drying.
Described Cornu Bubali dry extract is a water intaking Cornu Bovis seu Bubali thin slice, adds 6-10 times of water gaging, decocts 1-3 time, and each 5-10 hour, collecting decoction filtered, and filtrate is condensed into thick paste, makes 80 ℃ of following dryings.
Each is powerful for component of the present invention: pseudo-ginseng blood-circulation-invigovating blood stasis dispelling, reducing swelling and alleviating pain have the power of strengthening by means of tonics concurrently; The Cornu Bubali clearing away heart-fire detoxification, removing heat from blood blood stasis removing dissipating rashes; Moschus, the refreshment of Borneolum Syntheticum causing resuscitation with aromatic drugs, pain relieving spasmolytic; The Venenum Bufonis removing toxic substances and promoting subsidence of swelling, the pain relieving heart tonifying; Sodium cholate can promote the digestion and the absorption of fat, activates the pancreas digestive enzyme; Calculus Bovis, Margarita removing heat from the heart to restore the consciousness, tranquilizing mind, spasmolytic; The Radix Ginseng strongly invigorating primordial QI, Yiqi and vein recovery.All medicines share has blood circulation promoting and blood stasis dispelling, invigorates vital energy and reinforce the heart the merit that centering is calmed the nerves.Work in coordination with mutually and useful antagonism by medicine in the prescription of the present invention, can improve blood circulation, coronary artery dilator increases coronary artery blood flow, improves myocardial ischemia; The formation and the progress of energy blood fat reducing or inhibition atheromatous plaque, or regressive effect is arranged, lower coronary resistance, adjust heart rate, bring high blood pressure down; Reduce the myocardial metabolism level, lower myocardial oxygen consumption, thereby myocardial ischemia is improved, angina pectoris is eased or eliminates, and cardiac function is improved; And when design component, adopting sodium cholate in a large number, and the ratio of corresponding other component of control has reduced the cost of product as far as possible when not reducing drug effect, cost performance of product is significantly increased, and has alleviated patient's financial burden.
Below, the pharmacological action of Chinese medicine composition of the present invention is described by zoopery:
1 medicine: " preparation of the present invention " pill for getting by the embodiment of the invention 1 preparation; JIUXIN DAN is that Japan rescues the production of heart Pharmaceutical Co., Ltd, and specification is 15 a milligrams/ball.
2 experimental techniques and result
2.1 acute toxicity test
Get 60 of healthy mices, evenly be divided into two groups, give " preparation of the present invention " and JIUXIN DAN 50mg/10g respectively and irritate stomach, observe toxic reaction and death toll by sex, body weight.
After " preparation of the present invention " and Japanese JIUXIN DAN are irritated stomach, the poisoning symptom difference of white mice, JIUXIN DAN mainly shows the central excitation phenomenon, occurs the clonic spasm type then and faints from fear, and faints from fear because of tetanic type at last and opisthotonus causes death." preparation of the present invention " be mainly performance maincenter inhibition then, and animal peace and quiet, the movable minimizing occur drowsiness phenomenon then, but righting reflex exist still.The mortality rate of JIUXIN DAN, " preparation of the present invention " is respectively 65%, 0%.The toxicity of Japan's JIUXIN DAN is bigger than " preparation of the present invention ", and there were significant differences.
2.2 rat action of the heart to isolated perfusion
Get 7 of the rat of growing up, the male and female dual-purpose, the head of fiercelying attack is cut the thoracic cavity open, takes out heart rapidly, puts in freezing kreb ' the s solution after the washing, inserts sleeve pipe from aorta, feeds O with 37 ℃ of kreb ' s solution constant voltage perfusions continuously to kreb ' s solution
2And CO
2Gas, and regulate both speed, make PH be constant at 7.4, put two small pieces filter paper at heart surface and connect electrocardio eeg amplifier recording ecg, get a bit of plastic tube, end is pricked a bead with plastic sheeting, put into left ventricle through left atrium, connect pressure transducer and link to each other, the record left ventricular pressure with YL-4 type pressure amplifier, and with pressure processor record left ventricular pressure climbing speed, with the MFV-1200 electromagnetic flowmeter record coronary flow of Japanese photoelectricity factory production.Above-mentioned four indexs are all traced continuously with the SJ-42 type 4 passage physiographs of Shanghai Medical Electric Instrument Factory production.Calculate administration front and back coronary flow, the left ventricular pressure climbing speed changes percentage rate, with its significance of t test determination.
The result: " preparation of the present invention " increases coronary flow effect highly significant (P<0.01), and makes left ventricular pressure and left ventricular pressure climbing speed obviously descend (P<0.05).
Below, the therapeutic effect and the safety of medicine of the present invention are described by the clinical drug development test:
1, case is selected:
" preparation of the present invention " clinical verification object is all by " diagnostic criteria for coronary heart disease ", electrocardiogram is ischemic change (ST-T change) case during based on rest, or there is classical angina to show effect, or myocardial infarction and old myocardial infarction case are arranged, investigate fraction arrhythmia and other heart disease case simultaneously.
Clinical symptoms performance situation: coronary heart disease, classical angina 66 examples, atypia angina pectoris 56 examples, arrhythmia 1 example, myocardial infarction 1 example, old myocardial infarction 1 example, pulmonary heart disease 1 example.
Follow situation: complicated hypertension 50 examples in 123 examples, merge hyperlipidemia 54 examples, complicated hypertension and hyperlipidemia 32 examples, complicated hypertension and arteriosclerosis 4 examples merge arteriosclerosis 3 examples, complication with diabetes 1 example
2, drug dose and observational technique:
Medicine and consumption: " preparation of the present invention " pill for getting by the embodiment of the invention 1 preparation, every heavy 20mg, each sublingual administration 2 balls, some cases 3 balls, every day 2 times, some cases every day 3 times, withdraw other medicaments for coronary disease during taking this medicine, also withdraw blood pressure lowering and blood lipid-lowering medicine generally speaking with hypertension and hyperlipemic patients.
Observational technique: static electrocardiogram before record is taken medicine, sublingual administration " preparation of the present invention " 2 balls immediately, take medicine back 1 hour, 2 hours, 24 hours respectively recording ecg change, be instant curative effect.Later on each buccal " preparation of the present invention " 2 balls, every day 2 times, two weeks is a course of treatment, treats 1-4 the course of treatment.Whenever expire a course of treatment, the check electrocardiogram once, relatively before and after electrocardiogram change, and measure heart rate, blood pressure situation, symptom variation and improvement situations such as inquiry angina pectoris, uncomfortable in chest, cardiopalmus, tachypnea, dizzy, perspiration.
Carry out thoracic cavity X line perspective before case begins to investigate, observe podiod and lung blood situation, in case in case of necessity, finish the course of treatment, carries out thoracic cavity X line check; All being diagnosed as merges the cerebral arteriosclerosis person, carry out the rheoencephalogram inspection; Make a definite diagnosis merging arteriosclerosis person and will carry out examination of ocular fundus; Blood fat respectively once, might checked triglyceride and protein electrophoresis under the condition simultaneously at the forward and backward serum cholesterol of checking as far as possible of treatment.
3, efficacy assessment standard:
Efficacy assessment standard is all evaluated according to " coronary heart disease, angina pectoris and ECG curative effect evaluation criteria ".Arrhythmia is by following standard rating.
The arrhythmia efficacy assessment standard:
Produce effects: treatment back electrocardiogram arrhythmia disappears, or premature beat is only arranged, the symptom person of being clearly better.
Effectively: treatment back electrocardiogram arrhythmia obviously reduces (general premature beat reduce to original more than 50%) and the symptom person of taking a favorable turn.
Invalid: treatment back arrhythmia does not have the changer.
Hypertension is according to " hypertension efficacy assessment standard " evaluation efficacy of antihypertensive treatment.
4, therapeutic outcome and efficacy analysis:
4.1 curative effect to treat angina pectoris: with classical angina 66 examples, effective 64 examples, effective percentage is 96.97%; Atypia angina pectoris 56 examples, effective 49 examples, effective percentage 87.5%, angina pectoris total effective rate 92.62%, treatment 122 example typical cases all have better curative effect with the atypia angina pectoris.See table 1 for details
Table 1 angina pectoris symptom efficacy analysis
4.2 cardiac function curative effect: the low caused various symptoms of cardiac function are all had the good curing effect, see (table 2) for details
The doing well,improving situation that table 2 cardiac function descends
4.3 ECG curative effect
Investigate in 123 cases, before the treatment during rest electrocardiogram pathological change 122 examples are arranged, visit check through the treatment observation, produce effects 26 examples account for 21.31%, improve 59 examples, account for 48.36%, total effective rate 69.67%, invalid is 30.33%, and statistical significant difference (P<0.05) is arranged between effective percentage and the inefficiency.
4.4 blood fat reducing effect:
Follow hyperlipidemia (54 examples of serum cholesterol>200mg%), serum cholesterol meansigma methods 247.33mg% before the treatment in 123 examples before the treatment.Treatment back meansigma methods is 220.23mg%, and 27.1mg% on average descends.Serum cholesterol changes before and after the treatment significant difference (P<0.05).
4.5 to following the hypertension effect:
50 examples are attended by the hyperpietic in 123 examples, and to begin the back 24 hours mensuration of taking medicine, produce effects 9 examples account for 13%, improve 13 examples, account for 27%, are 45% to following hyperpietic's total effective rate by " hypertension efficacy assessment standard "." preparation of the present invention " follows the hyperpietic that good hypotensive activity is arranged to coronary heart disease.
5, the observation of side effect
According to the 123 routine clinical investigation results of 5 medical institutions, in therapeutic process, do not find untoward reaction.
The specific embodiment
The present invention will be described in detail by the following examples.
Embodiment 1: the preparation of pill
Get the Radix Notoginseng of 1500 weight portions, be ground into coarse powder, use 80% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.0 with 20% hydrochloric acid solution, placement is spent the night, and filters, and filtrate is extracted with the ether jolting, discard ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol, at 60 ℃ of vacuum dryings, it is standby to make Radix Notoginseng total arasaponins; Water intaking Cornu Bovis seu Bubali thin slice adds 8 times of water gagings, decocts 2 times, and each 8 hours, collecting decoction filtered, and filtrate is condensed into thick paste, and it is standby to make Cornu Bubali dry extract 80 ℃ of dryings; Get the Cornu Bubali dry extract 55 weight portion pulverize separately of Radix Notoginseng 1500 weight portions and Moschus 5 weight portions, Calculus Bovis 40 weight portions, sodium cholate 200 weight portions, Venenum Bufonis 30 weight portions, Margarita 50 weight portions, Borneolum Syntheticum 40 weight portions, Radix Ginseng 500 weight portions, above-mentioned preparation; again with the Radix Notoginseng total arasaponins facing-up of above-mentioned preparation; sieve; mixing; with the general ball of ethanol; Radix Glycyrrhizae charcoal coating, cold drying promptly.
Embodiment 2: the preparation of capsule
Get the Radix Notoginseng of 9000 weight portions, be ground into coarse powder, use 50% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.0 with 30% hydrochloric acid solution, placement is spent the night, and filters, and filtrate is extracted with the ether jolting, discard ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol, at 80 ℃ of vacuum dryings, it is standby to make Radix Notoginseng total arasaponins; Water intaking Cornu Bovis seu Bubali thin slice adds 8 times of water gagings, decocts 2 times, and each 10 hours, collecting decoction filtered, and filtrate is condensed into thick paste, and it is standby to make Cornu Bubali dry extract 80 ℃ of dryings; Get the Cornu Bubali dry extract 180 weight portion pulverize separately of Radix Notoginseng 6000 weight portions and Moschus 5 weight portions, Calculus Bovis 40 weight portions, sodium cholate 180 weight portions, Venenum Bufonis 30 weight portions, Margarita 50 weight portions, Borneolum Syntheticum 40 weight portions, Radix Ginseng 200 weight portions, above-mentioned preparation; again with the Radix Notoginseng total arasaponins facing-up of above-mentioned preparation; cold drying; sieve; mixing; fill, make capsule.
Embodiment 3: the preparation of tablet
Get the Radix Notoginseng of 6000 weight portions, be ground into coarse powder, use 80% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.0 with 20% hydrochloric acid solution, placement is spent the night, and filters, and filtrate is extracted with the ether jolting, discard ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol, at 60 ℃ of vacuum dryings, it is standby to make Radix Notoginseng total arasaponins; Water intaking Cornu Bovis seu Bubali thin slice adds 8 times of water gagings, decocts 3 times, and each 8 hours, collecting decoction filtered, and filtrate is condensed into thick paste, and it is standby to make Cornu Bubali dry extract 80 ℃ of dryings; Get the Cornu Bubali dry extract 120 weight portion pulverize separately of Radix Notoginseng 9000 weight portions and Moschus 20 weight portions, Calculus Bovis 40 weight portions, sodium cholate 200 weight portions, Venenum Bufonis 30 weight portions, Margarita 40 weight portions, Borneolum Syntheticum 40 weight portions, Radix Ginseng 500 weight portions, above-mentioned preparation; again with the Radix Notoginseng total arasaponins facing-up of above-mentioned preparation; cold drying; sieve; mixing is granulated drying; add magnesium stearate, be pressed into tablet.
Embodiment 4: the preparation of granule
Get the Radix Notoginseng of 3000 weight portions, be ground into coarse powder, use 60% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.2 with 25% hydrochloric acid solution, placement is spent the night, and filters, and filtrate is extracted with the ether jolting, discard ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol, at 60 ℃ of vacuum dryings, it is standby to make Radix Notoginseng total arasaponins; Water intaking Cornu Bovis seu Bubali thin slice adds 9 times of water gagings, decocts 2 times, and each 6 hours, collecting decoction filtered, and filtrate is condensed into thick paste, and it is standby to make Cornu Bubali dry extract 80 ℃ of dryings; Get the Cornu Bubali dry extract 60 weight portion pulverize separately of Radix Notoginseng 4000 weight portions and Moschus 8 weight portions, Calculus Bovis 48 weight portions, sodium cholate 80 weight portions, Venenum Bufonis 40 weight portions, Margarita 120 weight portions, Borneolum Syntheticum 130 weight portions, Radix Ginseng 400 weight portions, above-mentioned preparation; again with the Radix Notoginseng total arasaponins facing-up of above-mentioned preparation; sieve; mixing; granule is made in cold drying
Embodiment 5: preparation of soft capsule
Get the Radix Notoginseng of 7500 weight portions, be ground into coarse powder, use 90% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.0 with 30% hydrochloric acid solution, placement is spent the night, and filters, and filtrate is extracted with the ether jolting, discard ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol, at 90 ℃ of vacuum dryings, it is standby to make Radix Notoginseng total arasaponins; Water intaking Cornu Bovis seu Bubali thin slice adds 10 times of water gagings, decocts 3 times, and each 10 hours, collecting decoction filtered, and filtrate is condensed into thick paste, and it is standby to make Cornu Bubali dry extract 80 ℃ of dryings; Get the Cornu Bubali dry extract 100 weight portion pulverize separately of Radix Notoginseng 7500 weight portions and Moschus 12 weight portions, Calculus Bovis 25 weight portions, sodium cholate 240 weight portions, Venenum Bufonis 45 weight portions, Margarita 110 weight portions, Borneolum Syntheticum 150 weight portions, Radix Ginseng 300 weight portions, above-mentioned preparation; again with the Radix Notoginseng total arasaponins facing-up of above-mentioned preparation; sieve; add an amount of Polyethylene Glycol-400 and a spot of glycerol; mixing is pressed into soft capsule.
Embodiment 6: the preparation of powder
Get the Radix Notoginseng of 9000 weight portions, be ground into coarse powder, use 30% alcohol reflux, filter, filtrate decompression is concentrated into no ethanol flavor, transfers PH to 6.5 with 15% hydrochloric acid solution, placement is spent the night, and filters, and filtrate is extracted with the ether jolting, discard ether solution, use water saturated n-butanol extraction, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol, at 30 ℃ of vacuum dryings, it is standby to make Radix Notoginseng total arasaponins; Water intaking Cornu Bovis seu Bubali thin slice adds 6 times of water gagings, decocts 1 time, and each 5 hours, collecting decoction filtered, and filtrate is condensed into thick paste, and it is standby to make Cornu Bubali dry extract 60 ℃ of dryings; Get the Cornu Bubali dry extract 200 weight portion pulverize separately of Radix Notoginseng 1000 weight portions and Moschus 20 weight portions, Calculus Bovis 20 weight portions, sodium cholate 70 weight portions, Venenum Bufonis 15 weight portions, Margarita 30 weight portions, Borneolum Syntheticum 80 weight portions, Radix Ginseng 200 weight portions, above-mentioned preparation; again with the Radix Notoginseng total arasaponins facing-up of above-mentioned preparation; sieve; mixing; powder is made in cold drying.