CN1651067A - Medicinal composition for treating and/or preventing heart brnin blood vessel disease and its preparation method - Google Patents
Medicinal composition for treating and/or preventing heart brnin blood vessel disease and its preparation method Download PDFInfo
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Abstract
A Chinese medicine in the form of injection or others for preventing and treating cardiovascular and cerebrovascular diseases, such as cerebral arteriosclerosis, cerebral infarction, apoplexy, coronary atherosclerosis, coronary heart disease, angina pectoris and myocardial infaction, is prepared from ginseng, astragalus, ganoderma and leech.
Description
Technical field
The invention belongs to technical field of Chinese medicines, specifically, the present invention relates to a kind of cerebral arteriosclerosis that treats and/or prevents, the Chinese medicine composition of cardiovascular and cerebrovascular diseases such as cerebral infarction, apoplexy, coronary atherosclerosis and the coronary heart disease that causes thereof, angina pectoris, myocardial infarction, its preparation, particularly freeze-dried powder and oral liquid formulations, and their preparation method.
Background technology
Modern study proves, cerebral arteriosclerosis, cerebral infarction, coronary heart disease, angina cordis, myocardial infarction, belong to cardiovascular and cerebrovascular disease, this type of sick high incidence at present, high relapse rate, high disability rate, all bring huge financial burden for society and family, have a strong impact on the middle-aged and elderly people life quality.
At present, have much suit in the medicine of clinical diagnosis and treatment as: FUFANG DANSHEN PIAN, XINNAOKANG, DIEMAILING ZHUSHEYE etc. different therapeutic effect is all arranged, but curative effect are all not ideal enough.
Theory and practice according to Chinese medicine, active component in the Radix Ginseng mainly is the ginsenoside, known ginsenoside can reduce mice brain and myocardium lactic acid content under the severe ischemic anaerobic condition, and have protection heart muscle capillary endotheliocyte and the effect that alleviates mitochondrial injury, can protect in the ischemic myocardium superoxide dismutase activity and reduce myocardial lipid peroxide content; The ginsenoside also can reduce the generation of acute cerebral ischemia animal brain apoplexy.The Radix Astragali has blood vessel dilating, the effect of coronary artery dilator.Cerebral anoxia there is significant antagonism, can obviously prolongs the time-to-live of mice.Ganoderma obviously reduces coronary resistance, and coronary flow is increased, and ischemic myocardium is had protective effect, has antiplatelet aggregative activity simultaneously.Hirudo has strong anticoagulation and very strong fibrinolytic effect, and platelet aggregation is had significant inhibitory effect, and atheromatous plaque is had tangible regressive effect.
The inventor is according to the theory and the method for treatment rule of treatment of Chinese medicine treatment, prevention cardiovascular and cerebrovascular disease, select for use above-mentioned inrigorating qi and promoting blood circulation Chinese medicine Radix Ginseng, the Radix Astragali, Ganoderma, Hirudo to make the pharmaceutical composition that treats and/or prevents cardiovascular and cerebrovascular disease, obtained ideal therapeutic effect.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition that treats and/or prevents cardiovascular and cerebrovascular disease, said composition contains Radix Ginseng, the Radix Astragali, Ganoderma and Hirudo, and the ratio of the parts by weight of described each component is a Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=50-150: 100-450: 100-450: 1-5.Also can contain in the said composition known treat cardiovascular and cerebrovascular disease, do not have the Chinese medicine of adverse effect with above four kinds of compositions, Radix Salviae Miltiorrhizae etc. for example.Radix Ginseng in the said composition can also with other join class for example Radix Ginseng Rubra etc. substitute, should contain a certain amount of ginsenoside in order to other ginseng class that replaces Radix Ginseng.
Preferred, the ratio of the parts by weight of wherein said each component is a Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=50-150: 100-300: 100-300: 1-2.More preferably Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=100: 300: 300: 1.5.
Another object of the present invention has provided the various pharmaceutical formulations made from pharmaceutical composition of the present invention, for example oral formulations or injection, and oral formulations is oral liquid, tablet, granule and capsule etc. for example.Injection is water preparation, suspension, freeze-dried powder etc. for example.The particularly preferred oral formulations of the present invention is an oral liquid; Particularly preferred injection is aqueous injection or freeze-dried powder, and described freeze-dried powder can be used for intravenous injection or intravenous drip.
Pharmaceutical composition of the present invention and various preparation thereof are used for the treatment of and/or prevent cardiovascular and cerebrovascular disease, and for example cerebral arteriosclerosis, cerebral infarction, coronary heart disease, angina cordis, myocardial infarction etc. have good effect.The cardiovascular disease chest pain that pharmaceutical composition of the present invention and various preparation cause coronary heart disease, uncomfortable in chest, cardiopalmus, breathing hard has significant therapeutic effect; reperfusion injury has significant protective effect to acute myocardial ischemia; and can dwindle myocardial infarction and/or cerebral infarct size, improve brain arteries and veins sclerosis aroused in interest, cerebral blood supply insufficiency.Do not have patient's low dose of manifest symptom to use obviously relief of symptoms of said composition and various preparation, significantly reduce the possibility of acute attack, improve patient's life quality effectively.
Another object of the present invention has provided preparation of drug combination method of the present invention, and this method comprises:
(1) Radix Ginseng is used 75% ethanol extraction, it is standby to concentrate the back;
(2) with the Radix Ginseng residue of step (1) with the Radix Astragali, Ganoderma, use water boiling and extraction, extracting solution adds 10% aqua calcis and transfers to pH12.0, after leaving standstill 1 hour, add sulfuric acid solution pH is transferred to 5.0, left standstill 4 hours, get supernatant concentration, filter, and pressure sterilizing;
(3) Hirudo is used water boiling and extraction, concentrated extracting solution with the concentrated solution ethanol dilution, filters, and concentrates, and removes ethanol;
(4) product with above each step mixes, and obtains pharmaceutical composition of the present invention.
The method of pharmaceutical composition of the present invention being made various preparations can adopt the various known preparation techniques of pharmaceutical field, various general equipment, and the auxiliary material of various routines such as carrier, diluent, excipient wait and finish.
For example, the product that obtains with said method can further be processed into and be suitable for the preparation that various routes of administration are used.As with the routine techniques of resulting above-mentioned composition, use conventional carrier and/or excipient further to make oral liquid, tablet, granule and capsule according to pharmaceutical field.
Under the situation of preparation oral liquid, with the compositions dilute with water that said method obtains, the centrifugal supernatant of collecting discards precipitation, uses filter paper filtering then, and add an amount of water and regulate concentration, packing, sterilization promptly gets oral liquid formulations; Or with the 2nd and the extract cycles of concentration of the 3 two step suitably reduce, it is centrifugal that the product of (1), (2) and (3) step merges the back, filter paper filtering adds an amount of water and regulates concentration, packing is sterilized, and promptly gets oral liquid formulations.Perhaps
Make injection according to conventional method, for example, aqueous injection or freeze-dried powder.For example, under the situation of preparation freeze-dried powder, can add water for injection in the compositions that said method obtains, filter through mocromembrane then, packing in lyophilizing below-45 ℃, is made freeze-dried powder.Before use, this freeze-dried powder with an amount of 5% glucose or the dilution of 0.9% sodium chloride solution, promptly be can be used for intravenous injection or intravenous drip.Under the situation of preparation aqueous injection, the present composition is diluted with water to suitable concentration, bottling, sterilization can obtain aqueous injection of the present invention.
Test such as the pyrogen of injection of the present invention, haemolysis, anaphylaxis and every physical and chemical index check result meet Chinese Pharmacopoeia version injection in 2000 and stipulate with purgation.
The advantage of preparation method of the present invention be can effectively extract and the medical material of purifying in contained effective active matter saponin, polysaccharide etc., especially under the situation of freeze-dried powder, effective active matter changes hardly behind-45 ℃ of low-temperature freeze dryinies, plays a role thereby make it directly enter blood through vein.
More specifically, can prepare according to following method:
1, Radix Ginseng is pulverized the back with 75% ethanol extraction 1-3 time, the extracting solution that merges is concentrated into does not have pure the flavor, obtains concentrated solution (1);
2, Radix Ginseng residue after step 1 extraction and the Radix Astragali and the Ganoderma after the pulverizing are added the water that 5-10 doubly measures, decoct and extract 1-3 time, merge extractive liquid, transfers to pH12.0 to wherein adding 10% aqua calcis, leaves standstill 1 hour; Add sulfuric acid solution again and transfer to pH5.0, left standstill 4 hours; Draw supernatant, be condensed into the clear paste of relative density 1.00-1.05 (50 ℃), filter, in the 500ml saline bottle, 115 ℃ of sterilizations in 30 minutes of hot pressing were left standstill 14 days, obtained extracting solution (2) with the filtrate embedding;
3, Hirudo powder is broken into powder, adds 4-8 times of water gaging and decoct extraction 1-3 time, merge extractive liquid, also is condensed into the clear paste that relative density is 1.00-1.05 (50 ℃), add ethanol to containing alcohol amount 75%, leave standstill 24 hours after-filtration, concentrated filtrate, reclaiming ethanol to filtrate does not have the alcohol flavor, obtains extracting solution (3);
4, concentrated solution (1) is mixed with extracting solution (2) and (3), obtain pharmaceutical composition of the present invention;
5, above-mentioned composition is added the injection water to certain volume, be sub-packed in the glass tube vial after mocromembrane filters, lyophilizing under-45 ℃ or lower temperature promptly obtains freeze-dried powder of the present invention; Or
6, the present composition is diluted with water to suitable concentration, is sub-packed in the peace bottle, sterilization can obtain aqueous injection of the present invention.
7, with the above-mentioned composition dilute with water, the centrifugal supernatant of collecting discards precipitation, uses filter paper filtering then, and add an amount of water and regulate concentration, packing, sterilization promptly gets oral liquid formulations of the present invention.
The toxicity test that the inventor carries out the present composition and preparation thereof, the test of pesticide effectiveness and clinical observation treatment show that safety of medicine of the present invention is reliable, stable curative effect.
Test the research of 1 acute toxicology
Give the acute toxic reaction situation that produced behind the mice by this laboratory observation present composition, for clinical application provides reference.
Experiment material
Animal: Kunming mouse, body weight 19-21g (6-8 age in week), male and female half and half, laboratory animal room provides by new drug pharmacological research center, Shandong Province.
Experimental drug: the freeze-dried powder of the embodiment of the invention 4,0.3g/ props up, and dilutes debita spissitudo with 0.9% sodium chloride injection during experiment.
Method and result
Get 60 of healthy mices, male and female half and half are divided into six groups at random, and by geometric ratio dosage preparating liquid, tail intravenously administrable, volume are 0.1ml/20g, observe the living or death situation of animal in the week, write down the dead animal number every day.The result calculates by the Sun Shi synthetic method and injects the heart health LD that requires mental skill
50Be 15.18g/kg, 95% the average credible 15.18 ± 2.01g/kg that is limited to.
Test 2 chronic toxicity researchs
Experiment material
Animal: the Wistar rat, body weight 70-90g, male and female half and half, laboratory animal room provides by new drug pharmacological research center, Shandong Province.
Experimental drug: the freeze-dried powder of the embodiment of the invention 4,0.3g/ props up, and dilutes debita spissitudo with 0.9% sodium chloride injection during experiment.
Experimental technique
Get 60 male and female half and half of healthy Wistar rat, be divided into 4 groups at random, be provided with 3.0,1.5,0.75g/kg, volume is three dosed administration groups of 10ml/kg, and administration volume 1ml/100g matched group gives equal-volume 0.9% sodium chloride injection.Every day 1 time, successive administration 90 days.Claimed a body weight in per 10 days in 30 days, after 30 days, claimed a body weight in every month, after time administration 24 hours, each group was all got 10 rats, sacrificed by decapitation, and routine blood test, hepatic and renal function are done in blood sampling simultaneously.Cut open core, liver, spleen, lung, kidney put in 10% formalin solution fixing, paraffin embedding, section is with the rearmounted microscopically tissues observed of hematoxylin eosin stain morphological change.
The result shows, this medicine does not all have the food-intake of animal subject experimental session, hair growth promoting growth, breath cycle, defecate etc. obviously influences every physiochemical indice, each main organs and biochemical measurement index compare no significant difference with matched group, do not find toxicity, show that the present invention is safe and reliable.Test 25-100 that used drug dose calculates suitable clinical dosage by kg body weight doubly.
Above result shows, be injected 25-100 times that is equivalent to clinical consumption to trying rat, no obvious toxicity takes place, give once-a-day by the healthy normal person who is tested, one time 5 (1.5g) adds among 5% glucose or the 0.9% sodium chloride injection 300ml, drips speed 60/1 minute, continuous use one month, no obvious adverse reaction takes place, and main organs and biochemical investigation index all do not have obvious change.Clinical observation shows that patient does not see obvious adverse reaction after using 1-2 the course of treatment.Show that in the clinical use of this medicine be safe.
Test of the protective effect of 3 present compositions to myocardial ischemia reperfusion injury.
Reperfusion injury has significant protective effect to the present composition to the experimental dog acute myocardial ischemia, and can dwindle myocardial infarction area.
Experimental technique:
1, select 20 of healthy hybrid dogs, male and female are not limit, and after body weight 11-15Kg raises a week, are divided into four groups at random, 5 every group, matched group are set, high, medium and low three dosage observation groups respectively.After determining group, each group is all used under the pentobarbital sodium 30mg/kg intravenous anesthesia, the 4th intercostal is opened breast in the left side, the ligation left coronary artery anterior descending branch mid point of fighting, or maximum oblique angle props up root, cause acute myocardial infarction, behind the ligation arteria coronaria 30 minutes, each group gives from external jugular vein respectively: matched group gives 0.9% sodium chloride injection by every 2ml/kg, administration observation group presses: 80mg/kg, 40mg/kg, three dosage of 20mg/kg, quiet of the speed that per minute is 60, the test medication is the freeze-dried powder of embodiment 4.
2, the collection of data, each experimental group animal is all at left common carotid artery intubate and ventricle interpolation pipe, through transducer pressure is converted to the signal of telecommunication, with going into to lead monitor (Rm-6000 Japan electric light) recording blood pressure, left ventricular pressure and a time-derivative thereof, separation ascending aorta and left coronary artery circle round and prop up, put the flow transducing head, with electromagnetic flowmeter (MFV-1200 Japan electric light) record aorta and coronary flow, collect the following data, heart rate, left ventricular systolic pressure, the maximum climbing speed of intraventricular pressure, the maximum fall off rate of intraventricular pressure, ventricular end diastolic pressure, the aorta flow, stroke volume, coronary flow etc.
3, myocardial infarction area is measured, and after the experimental data collection finishes, puts to death animal, with the blue method dyeing of nitro tetrazole heart, measures myocardial infarction area with weight method.
Press following formula calculating myocardium infarct size:
Infarct cardiac muscle weight/left ventricular mass * 100%
The results are shown in Table 2.
Table 2, the present composition are to the protective effect of myocardial ischemia reperfusion injury
Anxious myocardial ischemia-reperfusion bleeding from anus mechanical index the recovery rate (* % ± S) that surges
| Matched group | Experimental group | |||
| ????(20mg/L) | ????(40mg/L) | ????(80mg/L) | ||
| Heart rate HR | ????79.86±4.18 | ????85.96±5.96 | ????88.16±4.92 * | ????85.54±3.12 ** |
| Aortic systolic pressure ASP | ????76.18±1.81 | ????78.86±3.18 * | ????83.01±4.98 * | ????86.08±4.16 ** |
| Left ventricular systolic pressure peak L VSP | ????75.26±1.98 | ????80.16±3.54 * | ????80.15±3.16 * | ????89.45±3.96 ** |
| LVEDP is not pressed in left side chamber diastole | ????142.86±14.87 | ????141.142.12±11.32 | ????127.05±13.54 * | ????124.06±16.54 |
| Maximum climbing speed+the dp/dtmax of left indoor pressure | ????58.01±4.15 | ????71.06±9.15 * | ????72.02±10.66 * | ????81.54±4.28 |
| Maximum fall off rate-the dp/dtmax of left indoor pressure | ????56.96±4.62 | ????63.02±1.78 * | ????73.98±13.45 * | ????85.02±10.54 ** |
| Cardiac output CO | ????53.54±2.89 | ????59.559.54±3.08 ** | ????62.01±4.98 ** | ????76.45±3.88 ** |
Experimental group and matched group are relatively
*P＜0.05
*P＜0.01
Test the therapeutical effect of 4 present compositions to myocardial ischemia
Experimental technique:
1, select 25 of healthy Wistar rats, male and female have concurrently, and body weight 220-300g raised after three days, was divided into 5 groups at random, 5 every group.C is set: Sham-operated control group respectively, A: ischemia group, B: acute administration group (ischemia group A myocardial ischemia administration after 60 minutes, tail vein shot 80mg/kg dosage), D: perfusion group again (ischemia was irritated after 40 minutes 20 minutes again), E: chronic administration group (perfusion group was again pressed the 20mg/kg dosed administration three days)., the test medication is the freeze-dried powder of embodiment 4.After determining grouping, each group is all at Nembutal vein anesthetic, the descending open chest surgery of artificial respiration, the ligation ramus descendens anterior arteriae coronariae sinistrae causes acute myocardial infarction, all animal via cardioelectric monitors, experiment finishes from abdominal aortic blood, blood plasma low-temp storage t-PA to be measured and PAI activity, heart preparation measuring and calculating myocardial infarct size.
2, the collection of data, t-PA and PAI activity all adopt the chromophoric substrate algoscopy, and medicine box is from Shanghai Medical Univ's Molecular Genetics Lab.Blood plasma and arteria coronaria effluent t-PA activity represent with Iu/ml and miu/ml that respectively PAI active unit represents with Au/ml.
3, the mensuration of myocardial infarction area after the experimental data collection finishes, is put to death animal, with nitro tetrazole method dyeing heart, measures myocardial infarction area with weight method.
Calculate by following fraction:
Infarct cardiac muscle weight/left ventricular mass * 100%
The result shows that obviously the activity of histiotype plasminogen activator (t-PA) the PA inhibitor (PAL) that reduces can return to the preceding level of ischemia, and myocardial infarction area significantly dwindles, and early quantity is obvious to demonstrate administration time.See Fig. 1.
Test the therapeutical effect of 5 present compositions to cerebrum ischemia
Experimental technique:
1, select 15 of healthy hybrid dogs, male and female have concurrently, and body weight 12-15kg is divided into 3 groups after raising a week at random, 5 every group, matched group is set, two dosed administration observation groups of 60mg/kg, 30mg/kg.The test medication is the freeze-dried powder of embodiment 4.After determining group, each group is all anaesthetized the back in femoral arteriography with pentobarbital sodium 30mg/kg intravenously administrable, and through pressure transducer AP-621G carrier amplifier, record systolic arterial pressure and relaxing period pressure, and record standard II lead electrocardiogram are to measure heart rate.Separate common carotid artery and external carotid artery and fight, the ligation external carotid artery causes the experimental cerebral ischemia type, and the internal diameter electromagnetic flowmeter probe placement that will suit is in common carotid artery, by MF-27 type electromagnetic flowmeter determination ICAF, as cerebral blood flow.Measure the femoral artery blood flow as the peripheral blood flow with method, postoperative was stablized 10 minutes, by RM-6000 how logical physiograph record These parameters be data before the medication.
2, the collection of data
Matched group gives 0.9% sodium chloride injection, two dosage of 60mg/kg, 30mg/kg are pressed by administration observation group, after the dilution of 0.8% sodium chloride injection, import through multi-channel electronic pump vein, each group changes respectively at 1,5,10,20 and 30 minute duplicate record cerebral blood flow after the administration and PBF, and calculates cerebral vascular resistance and peripheral vascular resistance according to blood pressure.
Experimental result shows, can increase significantly during the experimental dog cerebral ischemia that the cerebral blood flow of dog and peripheral blood flow see Table 3, table 4.
Each test group dog cerebral blood flow variation comparison of table 3 (ml/min, X ± S)
| Group | Dosage | Before the medication | After the medication (min) | ||||
| ?????????1 | ????????5 | ??????????10 | ??????????20 | ????????30 | |||
| ??NS | ??1ml/kg | ??24.54±2.45 | ??23.86±2.78 | ???23.86±2.78 | ????23.88±2.54 | ????24.16±2.15 | ??24.45±2.06 **△△ |
| The present composition | ??60mg/kg | ??31.96±4.02 | ??47.02±5.70 **△△ | ???41.02±3.86 *△ | ????38.36±4.08 *△ | ????37.02±3.18 *△ | ??38.06±4.92 |
| The present composition | ??30mg/kg | ??42.54±2.45 | ??46.68±2.54 **△△ | ???45.86±1.54 ** | ????45.16±1.54 **△ | ????45.34±1.12 *△ | ??45.18±1.28△ |
Compare with the NS group
*P＜0.05
*Compare △ P＜0.05 △ △ P＜0.01 before and after P＜0.01 administration group medication
Each test group dog peripheral blood flow comparison of table 4 (ml/min, X ± S)
| Group | Dosage | Before the medication | After the medication (min) | ||||
| ???????????1 | ??????????5 | ??????????10 | ?????????20 | ?????????30 | |||
| ??NS | ????1ml/kg | ????30.54±7.68 | ????30.16±7.88 | ????29.54±5.89 | ????30.08±5.54 | ????31.12±8.06 | ????31.54±9.28 |
| The present composition | ????60mg/kg | ????40.60±8.66 | ????50.11±11.45 **△△ | ????47.05±11.88△ ** | ????47.05±11.88△ ** | ????43.88±9.80△ | ????43.76±9.66△ |
| The present composition | ????30mg/kg | ????41.20±6.86 | ????44.02±6.54△△ | ????43.18±6.54△△ | ????43.18±7.66△ | ????42.68±6.76 | ????42.72±6.06 |
Compare with the NS group
*P＜0.05
*Compare △ P＜0.05 △ △ P＜0.01 before and after P＜0.01 administration group medication
Carried out clinical trial with the present composition, the basic skills of clinical trial is: 300 routine acute angina pectoris, myocardial infarction, Cerebral Infarction Patients have been carried out clinical observation treatment, established 100 examples simultaneously with the comparative study of sick kind.Diagnostic criteria according to first national internal medicine academic conference cardiovascular diseases special interest group suggestion use February in 1980.Tcm syndrome differentiation and typing: light disease belongs to the deficiency of vital energy (or deficiency of both QI and YIN) blood stasis phlegm stagnation syndrome type more, and serious symptom belongs to the deficiency of vital energy (or deficiency of both QI and YIN) blood stasis phlegm-heat type, the disease of common obvious deficiency of both QI and YIN of phase after being ill more.Therapeutic Method: the single freeze-dried powder with the embodiment of the invention 4 of observation group, once-a-day, a 1.5g (5) adds among 5% glucose or the 0.9% sodium chloride injection 300ml, quiet.1 month course of treatment.Matched group uses conventional anti-cardiovascular drugs treatment.
Clinical observation result is as follows:
1, the present invention's cardiovascular disease chest pain that coronary heart disease is caused, uncomfortable in chest, cardiopalmus, the curative effect total effective rate of breathing hard are 96%.
2, the curative effect to treat angina pectoris that coronary heart disease is caused is, slight obvious effective rate 56%, improvement rate 38%, total effective rate 94%; Moderate obvious effective rate 42%, improvement rate 34%, total effective rate 82%; Severe obvious effective rate 35%, improvement rate 61%, total effective rate 96%.
3, to the curative effect of cerebral arteriosclerosis, cerebral infarction.
The present invention is 93% to the total effective rate of brain arteries and veins sclerosis aroused in interest, cerebral blood supply insufficiency, cerebral infarction.
4, to the curative effect of myocardial infarction
The present invention is 88% to the curative effect total effective rate of myocardial infarction.
5, hemorheological variation (seeing Table 1) showed before and after the present invention treated, and treatment back patient's plasma viscosity etc. all has bigger improvement.
Table 1 the present invention is to hemorheological influence
| Before the treatment | After the treatment | The t value | The P value | |
| Plasma viscosity (mpa.s) | ??1.67±0.06 | ??1.32±0.07 | ????4.12 | ????＜0.01 |
| The low viscosity (mpa.s) of cutting of whole blood | ??8.67±0.05 | ??6.67±0.03 | ????1.17 | ????＜0.05 |
| Fibrinogen (g/l) | ??3.05±1.17 | ??2.42±0.89 | ????3.89 | ????＜0.01 |
| Packed cell volume (%) | ??49.57±5.06 | ??47.23±3.12 | ????0.05 | ????＜0.05 |
The P value: the statistical result diversity ratio is than decision content.
T value: T inspection statistics end value.
Dosage when compositions of the present invention is used for the treatment of cardiovascular and cerebrovascular disease, freeze-dried powder or aqueous injection with embodiment 4 are example, described preparation can be used for intravenous injection or intravenous drip, adult's dosage can be once-a-day, every day, 2-5 propped up, with 15 days be a course of treatment, generally need the medication 1-2 course of treatment or follow the doctor's advice.Using under the situation of oral formulations, adult's dosage can be a twice-daily, and every day, 1-2 propped up, with 15 days be a course of treatment, generally need the medication 1-2 course of treatment or follow the doctor's advice.When being used to prevent cardiovascular and cerebrovascular disease, its dosage should cut down according to the circumstance, preferred oral preparation during prophylactic, and the comparable therapeutic dose of its dosage reduces by half.
Description of drawings
Fig. 1 has illustrated that the present composition is to t-PA (histiotype plasminogen active matter, the IU/ml of unit), the active influence of PAI (PA inhibitor, the AU/ml of unit) in mice AMI (myocardial infarction) blood plasma.Wherein each test group is respectively: C, matched group, A, ischemia group, B, acute administration group, D, perfusion group again and E, chronic administration group.Symbol △ △ wherein and
*For diversity relatively indicates.
By this figure as can be seen, used the mice of the present composition, the histiotype plasminogen activator (t-PA) that obviously reduces behind its myocardial ischemia and the activity of PA inhibitor (PAL) can return to the level before the ischemia, myocardial infarction area significantly dwindles, and early quantity is obvious to demonstrate administration time.
The specific embodiment
In order further to set forth related product and the method for technology of the present invention, provided following embodiment.But, the scope that these embodiment do not limit the present invention in any way.
The preparation of embodiment 1 present composition 1
Raw material: Radix Ginseng 500g, Radix Astragali 1000g, Ganoderma 1000g, Hirudo 10g
Preparation method:
1, the Radix Ginseng powder is broken into the piece that is not more than about particle diameter 1.5cm, adds 5 times of amount 75% ethanol, the heating and refluxing extraction secondary, each 4 hours, merge extractive liquid, filtered, and concentrated and reclaimed ethanol, and it is standby to obtain concentrated solution (1);
2, the Radix Astragali and Ganoderma powder are broken to the piece of the about 1.5cm of diameter, merge with the medicine residues of Radix Ginseng of step 1, the decocting that adds 10 times of amounts boils three times, and each 1.5 hours, collecting decoction added 10% aqua calcis and regulates pH value to 12.0, leaves standstill 1 hour; Add sulfuric acid solution adjust pH to 5.0, left standstill 4 hours; Draw supernatant, be concentrated into the clear paste of relative density 1.00-1.05 (50 ℃), filter, filtrate pressure sterilizing 30 minutes left standstill 14 days, obtained extracting solution (2);
3, Hirudo powder is broken into fine powder, the decocting that adds 6 times of amounts boils three times, and each 1 hour, collecting decoction, being concentrated into relative density is the clear paste of 1.00-1.05 (50 ℃), adds ethanol and reaches 75% to containing the alcohol amount, leaves standstill 24 hours, filters, concentrated filtrate reclaims ethanol to there not being the alcohol flavor, obtains extracting solution (3);
4, with above-mentioned concentrated solution (1) and extracting solution (2) and (3) merging, obtain pharmaceutical composition 1 of the present invention, amount to 115g.
The preparation of embodiment 2 present compositions 2
According to the method identical, be that raw-material amount is with embodiment 8: Radix Ginseng 1500g, Radix Astragali 4500g, Ganoderma 4500g and Hirudo 12g, the preparation present composition 2 amounts to 450g.
The preparation of embodiment 3 present compositions 3
According to the method identical, be that raw-material amount is with embodiment 8: Radix Ginseng 1000g, Radix Astragali 3000g, Ganoderma 3000g and Hirudo 15g, the preparation present composition 3 amounts to 300g.
The preparation of embodiment 4 freeze-dried powders
Embodiment 3 resultant composition are added the injection water to 2000ml, be divided in the glass tube vial of 1000 7ml,, obtain 1000 freeze-dried powders of the present invention, every 0.3g dress in-45 ℃ of following lyophilizing.
The preparation of embodiment 5 aqueous injection
Embodiment 3 resultant composition are added the injection water to 10000ml, be divided in the peace bottle of 1000 10ml,, obtain 1000 aqueous injection of the present invention, every 10ml dress in 110 ℃ of following hot pressing sterilization in 30 minutes.
The preparation of embodiment 6 oral liquids
Raw material: Radix Ginseng 500g, Radix Astragali 1000g, Ganoderma 1000g, Hirudo 10g
Preparation method:
1, with the Radix Ginseng section, add 5 times of amount 75% ethanol, the heating and refluxing extraction secondary, each 4 hours, merge extractive liquid, filtered, and concentrated and reclaimed ethanol, and it is standby to obtain concentrated solution (1);
2, the Radix Astragali and Ganoderma powder are broken to the piece of the about 1.5cm of diameter, merge with the medicine residues of Radix Ginseng of step 1, the decocting that adds 10 times of amounts boils three times, and each 1.5 hours, collecting decoction added 10% aqua calcis and regulates pH value to 12.0, leaves standstill 1 hour; Add sulfuric acid solution adjust pH to 5.0, left standstill 4 hours; Draw supernatant, pressure sterilizing 30 minutes left standstill 14 days, obtained extracting solution (2);
3, Hirudo powder is broken into fine powder, the decocting that adds 6 times of amounts boils three times, and each 1 hour, collecting decoction, being concentrated into relative density is the clear paste of 1.00-1.05 (50 ℃), adds ethanol and reaches 75% to containing the alcohol amount, leaves standstill 24 hours, filters, concentrated filtrate reclaims ethanol to there not being the alcohol flavor, obtains extracting solution (3);
4, with above-mentioned concentrated solution (1) and extracting solution (2) and (3) merging, centrifugal with 4000 rev/mins of centrifuges, obtain supernatant, discard precipitation.
3, above-mentioned supernatant is filtered with filter paper pulp after, be diluted to 2000ml, be sub-packed in 100 10ml oral liquid bottles of anticipating, 110 ℃ of sterilizations in 30 minutes of hot pressing promptly, every content 20ml.
The oral formulations of the present composition also can be obtained through dilution by the compositions that embodiment 1 obtains.
By the description of above-mentioned explanation and specific embodiments, proved absolutely feature and the beneficial effect of the inventive method with respect to prior art.Those of ordinary skills are according to instruction of the present invention; particularly can be under the situation that does not deviate from essence of the present invention with reference to the specific embodiment of the present invention; embodiment of the present invention are done various modifications and variation, and these modifications and variation are all within protection scope of the present invention.
Claims (10)
1. treat and/or prevent the pharmaceutical composition of cardiovascular and cerebrovascular disease, said composition contains Radix Ginseng, the Radix Astragali, Ganoderma and Hirudo.
2. according to the pharmaceutical composition of claim 1, the ratio of the parts by weight of wherein said each component is a Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=50-150: 100-450: 100-450: 1-5.
3. according to the pharmaceutical composition of claim 2, the ratio of the parts by weight of wherein said each component is a Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=50-150: 100-300: 100-300: 1-2.
4. the pharmaceutical composition any according to claim 1-3, wherein said compositions can be made oral formulations or injection.
5. according to the pharmaceutical composition of claim 4, wherein said injection is freeze-dried powder or aqueous injection.
6. according to the pharmaceutical composition of claim 5, wherein said freeze-dried powder can be used for intravenous injection or intravenous drip.
7. according to the pharmaceutical composition of claim 4, wherein said oral formulations is an oral liquid.
8. any one the preparation of drug combination method of claim 1-7, this method comprises:
(1) Radix Ginseng is used 75% ethanol extraction, it is standby to concentrate the back;
(2) with the Radix Ginseng residue of step (1) with the Radix Astragali, Ganoderma, use water boiling and extraction, extracting solution adds 10% aqua calcis and transfers to pH 12.0, after leaving standstill 1 hour, add sulfuric acid solution pH is transferred to 5.0, left standstill 4 hours, get supernatant concentration, filter, and pressure sterilizing;
(3) Hirudo is used water boiling and extraction, concentrated extracting solution with the concentrated solution ethanol dilution, filters and concentrates;
(4) product with above each step mixes, and obtains pharmaceutical composition of the present invention.
9. preparation method according to Claim 8, wherein resultant composition can further be made and be suitable for oral preparation.
10. preparation method according to Claim 8 adds water for injection in resultant composition, makes aqueous injection through packing; Or after adding water for injection, filter through mocromembrane, packing in lyophilizing below-45 ℃, is made freeze-dried powder.
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| CNB2004101026560A CN100384439C (en) | 2004-12-29 | 2004-12-29 | Medicinal composition for treating and/or preventing heart brnin blood vessel disease and its preparation method |
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| CNB2004101026560A CN100384439C (en) | 2004-12-29 | 2004-12-29 | Medicinal composition for treating and/or preventing heart brnin blood vessel disease and its preparation method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744867A (en) * | 2008-12-08 | 2010-06-23 | 河北瑞生药业有限公司 | Soft capsules for treating apoplexy and preparation method thereof |
| CN104606464A (en) * | 2015-02-05 | 2015-05-13 | 南通大学 | Pharmaceutical composition for treating alzheimer disease |
| CN105076586A (en) * | 2014-05-15 | 2015-11-25 | 钱如力 | A Polypeptide lucid ganoderma tea and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1224614A (en) * | 1998-01-24 | 1999-08-04 | 倪德贵 | Medicine for preventing and curing cardiac and cerebral vascular diseases and its preparation |
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2004
- 2004-12-29 CN CNB2004101026560A patent/CN100384439C/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744867A (en) * | 2008-12-08 | 2010-06-23 | 河北瑞生药业有限公司 | Soft capsules for treating apoplexy and preparation method thereof |
| CN105076586A (en) * | 2014-05-15 | 2015-11-25 | 钱如力 | A Polypeptide lucid ganoderma tea and preparation method thereof |
| CN104606464A (en) * | 2015-02-05 | 2015-05-13 | 南通大学 | Pharmaceutical composition for treating alzheimer disease |
| CN104606464B (en) * | 2015-02-05 | 2018-01-23 | 南通大学 | A kind of pharmaceutical composition for treating Alzheimer disease |
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| CN100384439C (en) | 2008-04-30 |
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