CN1569150A - Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents
Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process Download PDFInfo
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- CN1569150A CN1569150A CN 200410022445 CN200410022445A CN1569150A CN 1569150 A CN1569150 A CN 1569150A CN 200410022445 CN200410022445 CN 200410022445 CN 200410022445 A CN200410022445 A CN 200410022445A CN 1569150 A CN1569150 A CN 1569150A
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Abstract
The invention provides a Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process, wherein the preparation is prepared mainly from Rhodiola rosea and Breviscapine.
Description
Technical field: the present invention relates to a kind of Chinese medicine preparation that is used for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, belong to the field of traditional Chinese medicine technology.
Background technology: coronary atherosclerotic heart disease (abbreviation coronary heart disease) is the most important chronic disease of present industrialized country.With the U.S. that 200,000,000 populations are arranged is example, and the number of dying from coronary heart disease every year reaches 600,000, is used for annual about 5,000,000,000 dollars of the expense of coronary heart disease diagnosis and treatment.Except economic loss, coronary heart disease is returned the loss that patient, family members and kith and kin bring spiritual aspect, so coronary heart disease is called as " first killer " of industrialized country.Many developing countries (comprising China) Incidence of CHD also constantly rises over nearly 20 years.Chief reason is that infectious disease is controlled, the change of life style and population life-span prolong.Cerebrovascular is called apoplexy again or apoplexy is one of most important cerebrovascular of most industrialized countries, and its mortality rate accounts for second or the 3rd of the full cause of the death of crowd.In China, Japan and some countries based on Asian Peoples, apoplexy is serious than coronary heart disease to crowd's the extent of injury.Particularly about 3/4 patient has labour force in various degree to lose among the cerebrovascular disease survivor, and severe disabled person accounts for 40%.Show according to statistics, the sickness rate of cardiovascular and cerebrovascular disease, prevalence and mortality rate increase with the growth at age, the M ﹠ M of the natural population of China more than 60 years old is higher, along with the quickening of aging process, China has stepped into aging society, and is more urgent for the needs of treatment cardiovascular and cerebrovascular diseases medicament, and the medicine that is used for cardiovascular and cerebrovascular disease that goes on the market at present, though Western medicine preparation is effective but toxic and side effects is bigger, untoward reaction is more, and the Chinese medicine preparation effect is also not ideal enough.The Chinese patent communique discloses name, and to be called " compound oral liquid preparation of alpine rhodiola root and preparation technology thereof ", application number be 93102898.1 patent application, it is made of in right amount Radix Rhodiolae, the Radix Astragali, Fructus Lycii and Mel, and description is introduced it effective activating brain cell, strengthen cardiovascular function, can make two-ways regulation, human body immunity improving ability, resisting fatigue, defying age to blood glucose, blood pressure.But we find that its effect is unsatisfactory in actual application; The Chinese patent communique discloses that name is called " healthful wine of rhodiola root ", application number is: 94107917.1 technology, this product are a kind of wine product, obviously are not suitable for the cerebrovascular patient and use; The Chinese patent communique discloses also that application number is 99102847.3, name is called " a kind of rhodiola rosea injection for the treatment of angina pectoris ", put down in writing in the application documents: its raw material is by separation and Extraction in the Chinese medicine Radix Rhodiolae, and main effective ingredient is rhodioloside and butyl alcohol.Pharmacological evaluation shows to have the obvious effect that improves dog acute myocardial ischemia and myocardial infarction, alleviates the myocardial damage degree, obviously reduces serum paraoxonase creatine phosphate kinase (CK) content, and obviously dilating coronary blood vessel reduces coronary resistance., effect rapid-action through the obstruction of qi in the chest and cardialgia (angina pectoris) that intravenously administrable or oral administration cause stagnation of heart-blood obviously, effect is lasting.But because single use Radix Rhodiolae experimental studies have found that what we carried out its effect is also undesirable as the preparation raw material; It is 03126742.4 that nearest Chinese patent communique discloses " a kind of rhodiola kirilowii Regel injectable powder and preparation method thereof " application number, this disclosure of the Invention a kind of rhodiola kirilowii Regel injectable powder, it is to be raw material after extraction, purification, an amount of pharmaceutic adjuvant allotment of adding with the Chinese herbal medicine rhodiola kirilowii Regel, be prepared from freeze-drying method, its main active is: rhodioloside, butyl alcohol and total flavones; This description is thought: the product stability that provides is good, effect duration is long, shows to have to resist myocardial ischemia significantly and treating cerebral ischemia that cardiovascular and cerebrovascular diseases such as coronary heart disease, cerebral infarction are had excellent curative through pharmacodynamics test.But because still single use Radix Rhodiolae finds that as the preparation raw material its effect is also unsatisfactory in the contrast experiment that we did.
Summary of the invention: the objective of the invention is to: provide a kind of and can treat Chinese medicine preparation of cardiovascular and cerebrovascular disease and preparation method thereof.The present invention constitutes like this: calculate according to components by weight percent: it mainly is prepared from by Radix Rhodiolae 600-1400 part and breviscapine (in the lamp-dish flower acetic that wherein contains) 20-60 part.Specifically: calculate according to components by weight percent: it is prepared from by 1000 parts of Radix Rhodiolaes and 40 parts of breviscapines (in lamp-dish flower acetic) and appropriate amount of auxiliary materials.Described adjuvant comprises according to the different dosage form of preparation: sucrose, dextrin, starch, polyacrylic resin, micropowder silica gel, carboxymethyl starch sodium, magnesium stearate, PEG-6000, mannitol.Preparation of the present invention comprises granule, hard capsule, soft capsule, tablet, drop pill, oral liquid, injection, comprising: injection, glucose infusion liquid, freeze-dried powder, slow releasing preparation, controlled release preparation etc.The preparation method of the Chinese medicine preparation of this treatment cardiovascular and cerebrovascular disease is: after Radix Rhodiolae being adopted the method effective component extracting of decocting in water or percolation, add breviscapine again and suitable adjuvant is prepared into different preparations.
Granule of the present invention can prepare like this: get Radix Rhodiolae and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste, adds breviscapine and sucrose, dextrin, and mixing is granulated, sieve, and drying, granulate, packing is promptly.The advantage of this dosage form is: comfortable taste, effect are rapidly; Volume is little, and take and transportation etc. makes things convenient for; Cost is low.
Capsule of the present invention can prepare like this: get Radix Rhodiolae and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste, and spray drying adds breviscapine and starch, mixing is granulated, and sieves, drying, granulate, coating, packing, that is, wherein coating material can prepare like this: get 1.8g polyacrylic resin and the abundant mixing of 95% ethanol 36ml, soak after 24 hours, filter, promptly.This dosage form advantage is: outward appearance is clean and tidy, and is beautiful, easily swallows; Dosage is accurate, the bioavailability height; Medicine stability is good; Production, transportation etc. are convenient.
Tablet of the present invention can prepare like this: get Radix Rhodiolae and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste, and spray drying adds breviscapine and micropowder silica gel, mixing is granulated, and sieves, drying, granulate adds carboxymethyl starch sodium and magnesium stearate, mixing, tabletting, the bag film-coat, promptly, wherein coating material can prepare like this: get the 9g polyacrylic resin, add 95% ethanol 170ml, soak 24 hours to all dissolvings, other gets 1.5gPEG-6000 and adds a small amount of hot water and make it dissolving, in the adding in the resin solution, stir evenly, filter, get final product.The advantage of this dosage form is: dosage is accurate, steady quality; Take, produce, transportation etc. is convenient; Medicine stability is good; Mechanization is produced, and output is big, and cost is little.
Drop pill of the present invention can prepare like this: get Radix Rhodiolae, be ground into coarse powder, add ethanol percolation, percolate reclaims ethanol, adds the water boil dissolving after concentrating, filter, filtrate concentrates the back with water saturated equal-volume sec-butyl alcohol extraction 3 times, the reclaim under reduced pressure sec-butyl alcohol, and filtrate is concentrated into dried, pulverize for fine powder, with the breviscapine mixing; Other gets PEG-6000 after being heated to fusion in the water-bath, adds said mixture, stirs evenly, and 80-90 ℃ of insulation dissolved in the cold liquid paraffin, and inhale and remove surface liquid paraffin, drying, promptly.The advantage of this dosage form is that onset is rapid, and curative effect is lasting, and dosage is accurate.
Injection of the present invention prepares like this: get Radix Rhodiolae, be ground into coarse powder, add ethanol percolation, percolate reclaims ethanol, add the water boil dissolving after concentrating, filter, filtrate concentrates the back with water saturated equal-volume sec-butyl alcohol extraction 3 times, the reclaim under reduced pressure sec-butyl alcohol, ethanol with ethanol elution, is reclaimed in the concentrated back of filtrate on polyamide chromatography post, eluent adds water boil after concentrating, filtrate is condensed into dense clear paste, adds breviscapine again and suitable adjuvant prepares injection, glucose infusion liquid, freeze-dried powder.
Injection can prepare like this: Radix Rhodiolae extract adds the injection water and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boils, and filters, and filtrate is regulated about pH to 6.5 with citric acid soln, filters clear and bright; Breviscapine adds the injection water and stirs evenly, and regulates pH to about 7.5 with sodium hydroxide solution, filters clear and brightly, and filtrate is mixed with above-mentioned Radix Rhodiolae extract solution, heat, and activated carbon adsorption, about adjusting pH to 6.5, filtration, embedding, promptly.
Glucose infusion liquid can prepare like this: Radix Rhodiolae extract adds the injection water and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boils, and filters, and filtrate is regulated about pH to 6.5 with citric acid soln, filter, Radix Rhodiolae extract solution; Breviscapine adds the injection water and stirs evenly, and regulates about pH to 7.5 with sodium hydroxide solution, filters, and filtrate and Radix Rhodiolae extract solution merge, regulate about pH6.5, and heating, filtrate for later use is filtered in activated carbon adsorption; After getting glucose and adding injection water boils dissolving, activated carbon adsorption, filtering decarbonization pumps into rare joining in the cylinder after clear and bright, adds above-mentioned Radix Rhodiolae extract and breviscapine filtrate, adds water to full dose, regulates about pH to 5.3, filters clear and brightly, and embedding is sterilized, promptly.
Freeze-dried powder can prepare like this: Radix Rhodiolae extract adds the injection water and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boils, and filters, and filtrate is regulated about pH to 6.5 with citric acid soln, filter, Radix Rhodiolae extract solution; Breviscapine adds the injection water and stirs evenly, and regulates about pH to 7.5 with sodium hydroxide solution, filters, and filtrate and Radix Rhodiolae extract solution merge, regulate about pH6.5, and heating, filtrate for later use is filtered in activated carbon adsorption; Get mannitol and add the injection water and boil dissolving, activated carbon adsorption, filtering decarbonization adds the above-mentioned mixed liquor of handling well, adds water to full dose, about adjusting pH to 6.5, filters clear and brightly, aseptic subpackaged, and lyophilization is sealed, promptly.
Intravenous injection provided by the invention has the characteristics that drug effect plays a role soon, bioavailability is high, is used for the severe case, relief of symptoms as early as possible, and the small-volume injection cost is low, is convenient to transportation and stores; The direct venoclysis of infusion solution has reduced the chance of secondary pollution, is convenient to clinical medical and nursing personnel's use; Freeze-dried powder stability is better, and transportation and preservation are convenient in anti-storage.
Compared with prior art, the present invention is that basic prescription is prepared from Radix Rhodiolae and breviscapine, has the QI invigorating warming YANG, blood circulation promoting and blood stasis dispelling, the effect of removing obstruction in the collateral to relieve pain; The compatibility of two kinds of medical materials has reasonable collaborative, synergic effect; The injection for preparing has the characteristics that the drug action performance is fast, bioavailability is high, especially for middle severe case, relief of symptoms as early as possible; It is remarkable especially that clinical trial certificate the present invention treats ischemia apoplexy and apoplexy sequela and chest arthralgia precordial pain syndrome curative effect.
According to theory of Chinese medical science, cardiovascular and cerebrovascular disease comprises cerebral infarction and apoplexy sequela and chest arthralgia precordial pain syndrome etc.; Chest arthralgia precordial pain syndrome, mainly by blood stasis due to qi deficiency, the visceral-qi deficiency, the gasification imbalance, blood operation in Tianjin is not smooth, is condensed into expectorant with the bringing about the spread of body fluid, the not smooth one-tenth stasis of blood of blood, expectorant stasis of blood impatency is due to heart arteries and veins is obstructed; Cerebral ischemia diseases is mainly disorderly contrary by QI and blood, and channels overflows broken, and blood oozing from the body openings or subcuta neous tissue is outside arteries and veins, and brains are injured, blood stasis, and expectorant is turbid, and diseases caused by retention of fluid gathers, and causes brain arteries and veins obturation, and unit is refreshing stranded, key machine obturation, the five internal organs lose system, and six internal organs are gas-tight, due to limbs are become estranged.Can select for use QI invigorating and body resistance strengthening medicine and drug for invigorating blood circulation and eliminating stasis prescription to control it.The traditional Chinese medical science is thought: " gas is that blood declines, Qi and blood deficiency, sering is not filled, qi depression to blood stasis ".The traditional Chinese medical science is also thought: kidney is the root of life, is the congenital foundation, and kidney is the root of the five internal organs, hides the essence of the five internal organs, kidney governing inspiration, and aerial root belongs to lung in kidney, so help air-breathing and respectful the falling of lung; Meet at kidney under the kidney-water ascending to coordinate with the heart, heart-fire, extreme misery mutual aid, then equilibrium between yin and yang; The kidney being the origin of congenital constitution, the spleen being the foundation of acquired constitution, and the strong fortune of spleen depends on the warm of kidney yang; The Liver and kidney part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels of living together, edema with the liver involved need rely moistening of kidney water foster, the kidney essense abundance, then liver also must nourish.The bladder master holds body fluid, and motive row water, but the gasification of bladder need the transpiration of kidney qi.Then cause a series of interactional strain processes of body if suffer from a deficiency of the kidney, so saying of " all kinds of diseases and ailments being born in kidney " arranged.The sick position of coronary heart disease is at the heart, and old complaint is at kidney, so suffering from a deficiency of the kidney is cause atherosclerosis, initiation coronary heart disease basic.Nourishing kidney-yin, kidney-replenishing, the kidney invigorating gas can stop atherosclerotic generation and development, thereby prevent and treat coronary heart disease.The above-mentioned cardiovascular and cerebrovascular disease of Chinese traditional treatment should use QI invigorating warming YANG or QI invigorating drugs for nourishing yin and activating blood circulation to dissipate blood stasis and dredge the collateral analgesic prescription to use it.
Radix Rhodiolae is a qi-restoratives medicine, has strengthening by means of tonics, kidney-replenishing, and the beneficial motive, blood circulation promoting and blood stasis dispelling, clearing away lung-heat to relieve cough, effects such as antipyretic analgesic are used to have a headache and fever, malaise, shortness of breath and palpitation, feeling of oppression and pain in the chest, diseases such as physical weakness; Breviscapine is the flavone component that extracts in the Herba Erigerontis, has blood circulation promoting and blood stasis dispelling, and the effect of removing obstruction in the collateral to relieve pain is used for apoplexy sequela, obstruction of qi in the chest and cardialgia (angina pectoris).But QI invigorating warming YANG behind the two medicine prescriptions, blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain is used for ischemia apoplexy and apoplexy sequela and chest arthralgia precordial pain syndrome (angina pectoris), meets theory of Chinese medical science, is rationally feasible.
According to modern medicine and pharmacology research and documents and materials, Radix Rhodiolae contains effective ingredient such as Radix Rhodiolae glycoside, flavonoid and several amino acids, has body-building, and is strong, the function in the degeneration-resistant border of enhancing body; Studies show that, Radix Rhodiolae has the human body immunity improving function, defying age, anti-hypoxia, resisting fatigue, radioprotective, cold resistance, anti-peroxidation, antiinflammatory, enhancing cardiac function improve the heart and brain blood flow, improve multiple effects such as myocardial ischemia, calmness, hypnosis, excited respiratory center; Breviscapine is the flavone component that is extracted by Herba Erigerontis; modern pharmacological research shows; breviscapine has the brain microcirculation of improvement; the cerebral blood flow increasing amount, protection cerebral tissue activities of antioxidant enzymes suppresses lipid peroxidation; alleviate the infringement of radical pair cerebral tissue; the ischemia-reperfusion cerebral tissue there is protective effect, increases myocardial flow, can block the Ca of myocardial cell
2+Passage reduces Ca
2+Interior stream reduces myocardial oxygen consumption, and ischemic myocardial is had protective effect; Have antiplatelet aggregation, blood viscosity lowering improves effects such as hemorheology.In the pharmacological toxicology research that we did, proved this two medicines prescription coupling, can remedy pharmacological action mutually and strengthen its pharmacological action mutually, made the above-mentioned cardiovascular and cerebrovascular disease of treatment more effective.
The applicant is an example with injection provided by the invention, and by pharmacological toxicology research, the result shows:
1, the anti-focal cerebral ischemia and the full brain blood test of pesticide effectiveness behind the two medicine prescriptions, than the effect enhancing of single medicine, experimental result sees Table 1,2,3.
Table 1 explanation breviscapine group can reduce model dog cerebral tissue ischemic region weight and ischemic tissue of brain percentage rate, and the Radix Rhodiolae group does not have this effect, and both strengthen in the effect of share.
Table 2 explanation breviscapine group can raise dog middle cerebral artery mean blood flow velocity and peak velocity, and this effect of Radix Rhodiolae group is not obvious, has more the effect of obvious increasing blood flow after both share.
Table 3 explanation Radix Rhodiolae group has obvious effect, and the effect of breviscapine group is not obvious, and both strengthen in the effect of share.
2, to the myocardial ischemia test of pesticide effectiveness, two medicines prescription has the better protection effect to myocardial infarction, and experimental result sees Table 4-13:
Table 4 explanation Radix Rhodiolae and breviscapine all can dwindle infarction size, and the Radix Rhodiolae group can significantly reduce animal pattern CPK, and the breviscapine group can significantly reduce LDH and the CPK of animal pattern.
Table 5-12 explanation Radix Rhodiolae group can be alleviated due to the model dog myocardial ischemia ST section and raises, and the breviscapine group has obvious or significant improvement effect to the decline of cardiac contractility ability (LVP and LV+dp/dt).
Table 13 explanation Radix Rhodiolae group can reduce the ischemic myocardium oxygen consumption.After two component compatibilities use, the scheming infarction of LAD ligation there is the better protection effect.
3, blood circulation promoting and blood stasis dispelling test has stronger change blood flow, thrombolytic effect than single medicine behind the two medicine prescriptions, antiplatelet aggregative activity, and experimental result sees Table 14-20:
Table 14-18 explanation Radix Rhodiolae group and breviscapine group all have the effect of the microcirculation of mouse auricle of improvement, and both obviously strengthen in the effect of share.
Table 19-20 explanation Radix Rhodiolae group and breviscapine group all have fibrin in the accelerate dissolution blood plasma, shorten the effect of fibrinolysis time, and the breviscapine group is better than the Radix Rhodiolae group, but no significant difference, both share the back effect and strengthen.
4, anti-stress test, this injection behind the prescription strengthens than single medicine effect, and experimental result sees Table 21-22:
Table 21-22 explanation Radix Rhodiolae group has obvious resisting fatigue and anti-normobaric hypoxia effect (p＜0.05), and breviscapine group effect not obvious (p＞0.05), both strengthen in the effect of share.
5, the LD50 of mouse peritoneal and intravenously administrable is respectively clinical plan with more than 900 times and 750 times of dosage respectively greater than 1200mg/kg and 1000mg/kg, and is as safe as a house, compares with single medicine, and the acute toxicity basically identical increases.
6, rat and Beagle Canis familiaris L. 12 girths poison result shows that toxicity and single medicine behind the two medicine prescriptions more do not increase.The clinical observation and the curative effect of treatment cardiovascular and cerebrovascular disease:
According to " medicine registration management way " and " specification requirement of new Chinese medicine clinical research ", adopt at random, positive drug parallel control, multicenter study scheme, for the safety and the clinical efficacy of this new drug treatment cardiovascular and cerebrovascular disease are estimated.
1. case choice criteria
1.1 diagnostic criteria
1.1.1 tcm diagnosis standard
1. formulate with reference to " the clinical research guideline of new Chinese medicine treatment apoplexy ".
2. formulate with reference to " the clinical research guideline of the new Chinese medicine treatment thoracic obstruction (angina pectoris) ".
1.1.2 differential diagnosis in tcm
1. 1. formulate with reference to 4.1.1-
2. 2. formulate with reference to 4.1.1-
1.1.3 Western medicine diagnose standard
1. " all kinds of cerebrovascular disease diagnosis main points " revised for the third time with reference to Chinese Medical Association in 1989 national cerebrovascular academic conference for the second time
A. transient ischemic attack
B. cerebral thrombosis
C. cerebral embolism
2. with reference to international heart association and association and World Health Organization's clinical name standardization associating special topic group report " name of ischemic heart desease and diagnostic criteria "
1.1.4 (classification) standard by stages
1. apoplexy standard by stages
A. acute stage: in 2 weeks of falling ill; B. convalescent period: fell ill for 2 thoughtful half a year; C. sequela stage: more than morbidity half a year.
2. thoracic obstruction weight grade scale (with reference to therapy of combining Chinese and Western medicine angina pectoris in 1979 and arrhythmia forum " angina pectoris and ECG curative effect evaluation criteria ")
1.2 include the case standard in
1. apoplexy is included the case standard in
The patients during acute stage that meets the apoplexy diagnostic criteria can be included the test case in.
2. the thoracic obstruction is included the case standard in
Have thoracic obstruction primary symptom, disease is disconnected clear and definite, meets differential diagnosis in tcm, and the twice above angina pectoris patient that show effect weekly can include the test case in.
2. observation index
2.1 safety observation
A. general health check-up project;
B. blood, urine, the just chemical examination of routine;
C. the heart, liver, kidney function test
2.2 health giving quality observation
1. apoplexy health giving quality observation
A. patient's mind, language and motor function;
B. nervous system signs;
C. examination of cerebrospinal fluid;
D. Cranial Computed Tomography scanning;
E. blood examination;
F. echoencephalography;
G. nuclear magnetic resonance check.
2. thoracic obstruction health giving quality observation
A. tcm symptom, the variation of tongue, arteries and veins is observed;
B. angina pectoris attacks time, number of times, degree, persistent period, induced factor, nitroglycerin dose;
C. Electrocardioscopy;
D. specific heart isozyme, lipids detection;
E. blood examination;
F. cardiac inspection;
G. exercise ECG inspection;
H. vectorcardiogram inspection;
I. dynamic ecg recordings examination;
J. standard cardioelectric figure checks.
3. curative effect determinate standard
3.1 apoplexy curative effect determinate standard
3.1.1 apoplexy point system
3.1.2 apoplexy efficacy assessment standard
Adopt the nimodipine method:
A. be almost recovered: 〉=85%. B. produce effects: 〉=50%. C. effective: 〉=20%. D. invalid:＜20%.
3.2 thoracic obstruction curative effect determinate standard
3.2.1 thoracic obstruction symptom criterion of therapeutical effect (with reference to therapy of combining Chinese and Western medicine angina pectoris in 1979 and arrhythmia forum " angina pectoris and ECG curative effect evaluation criteria ")
3.2.2 ECG curative effect evaluation criteria (with reference to therapy of combining Chinese and Western medicine angina pectoris in 1979 and arrhythmia forum " angina pectoris and ECG curative effect evaluation criteria ")
4. test method
240 patients that will meet selected condition are randomized into treatment group and matched group, and the treatment group is taken this medicine, must not use the medicine relevant with apoplexy, lasts for 2 weeks.
5. safety evaluatio
This test, the treatment group is observed 124 examples altogether, produce effects 56 examples wherein, effective 68 examples, invalid 19 examples, total effective rate 84.6%, viewing duration are not found toxicity, side effect and untoward reaction, result of the test confirms that this medicine treatment ischemia apoplexy and apoplexy sequela and chest arthralgia precordial pain syndrome are evident in efficacy, is safe and reliable new Chinese medicine.
Preparation for various dosage forms need be selected different adjuvants, technology for use, and we have also made experimental selection:
For granule:
Select sucrose+dextrin foundation (from mouldability, granule yield, cost):
| The investigation project | Adjuvant | ||
| Sucrose | Dextrin | Sucrose+dextrin (1.4: 1) | |
| Mouldability | Difference | Very | Very |
| Granule yield (%) | ????91 | ????96 | ????95 |
| Cost (unit/bag) | ????1.5 | ????3.1 | ????2.4 |
For capsule:
Select starch according to (from mouldability, granule repair to the angle, RH)
| The investigation project | Adjuvant | |
| Starch | Dextrin | |
| Mouldability | Very | Very |
| Granule repair to the angle (°) | ????35.5 | ????40 |
| ????RH(％) | ????54 | ????62 |
For tablet:
Select the foundation (from mouldability, repair, RH, disintegration) of micropowder silica gel+carboxymethyl starch sodium to the angle:
| The investigation project | Adjuvant | |||
| Blank | Starch | Micropowder silica gel | Micropowder silica gel+carboxymethyl starch sodium | |
| Mouldability | Difference | Generally | Very | Very |
| Granule repair to the angle (°) | ????47 | ????45 | ????37 | ????36.2 |
| ????RH(％) | ????76 | ????54 | ????31 | ????31.5 |
| Disintegration | ????123 | ????27 | ????11 | |
For drop pill:
Water extraction, ethanol refluxing process, percolation are selected three kinds of extracting method gained fluid extract mass ratioes:
Gained fluid extract amount rhodioside content
Extracting method
(ml)????????????????(mg/ml)
(1) decocting method 200 4.05
(2) ethanol reflux extraction 200 4.17
(3) percolation 200 4.33
The main effective ingredient of Radix Rhodiolae is a rhodioside, thus with the content of rhodioside as the index of weighing the extracting method quality, the result shows that the rhodioside content that water extraction and ethanol refluxing process extract is lower, and percolation content is the highest.Therefore, adopt the extracting method of percolation as this preparation.
For injection:
Radix Rhodiolae extract process for refining The selection result
The investigation project is 2. 3. sec-butyl alcohol extraction polyamide chromatography composite algorithm of polyamide chromatography method of sec-butyl alcohol extraction 1.
Rhodioside extract amount (ml) 100 100 100
Rhodioside content (mg/ml) 34.52 33.29 35.55
Extract solid content (mg/1ml) 341.2 334.6 274.4
Protein does not detect
Tannin does not detect
Resin does not detect
Oxalates does not detect
Potassium ion does not detect
Sec-butyl alcohol extraction polyamide chromatography composite algorithm effect is better, not only extract obtained content (purity) height, and also the solid content amount is much lower, therefore adopts sec-butyl alcohol extraction polyamide chromatography composite algorithm technology to make with extra care.
For glucose infusion liquid:
The isoosmotic adjusting agent prescription of design
Isoosmotic adjusting agent prescription consumption
The prescription composition
1??????????????????2
Radix Rhodiolae 10g 10g
Breviscapine (in lamp-dish flower acetic) 0.4g 0.4g
10% sodium hydroxide solution is an amount of
Sodium chloride/9g
Glucose 50g/
Water for injection adds to 1000ml 1000ml
The selection result:
The isoosmotic adjusting agent prescription is investigated the result
The investigation project
1????????????????????????2
The dark brown yellow clear liquid of the pale brown color clear liquid of appearance character
PH value 5.53 5.45
Rhodioside (mg/100ml) 3.37 3.40
Lamp-dish flower acetic (mg/100ml) 41.28 1.71
Sodium chloride (%)/96.21
Glucose (%) 99.26/
The result shows that prescription 2 usefulness sodium chloride adjustings etc. are oozed, and breviscapine content descends more than 90%, the medicinal liquid color burn; Prescription 1 usefulness glucose adjusting etc. is oozed, and does not influence active constituent content, and medicinal liquid is clear and bright, and color is not deepened yet.Therefore, select for use 5% glucose as isoosmotic adjusting agent.
For freeze-dried powder:
Mannitol uses separately, can play loose and hydrotropy effect simultaneously.
The excipient prescription of design:
Prescription numbering and consumption (in the 0.2g/ bottle) thereof
The supplementary material title
1????????????2???????????3
Radix Rhodiolae 1g 1g 1g
Breviscapine (in lamp-dish flower acetic) 40mg 40mg 40mg
Mannitol 120mg 60mg 170mg
10% sodium hydroxide solution is an amount of an amount of
Water for injection adds to 2.0ml 2.0ml 2.5ml
Preparation specification 0.20g 0.15g 0.25g
The selection result:
Projects are investigated the result
The investigation project
Prescription 1 prescription 2 prescriptions 3
It is yellow loose block, full, yellow block, not full, yellow loose block, fuller,
Appearance character
Do not see atrophy, the obvious atrophy of color and luster homogeneous, the slightly atrophy of color and luster heterogeneity, but color and luster heterogeneity
The dissolving situation is easily dissolved, brownish red clear liquid solubilized, and the brownish red clear liquid easily dissolves, the brownish red clear liquid
PH value 6.46 6.44 6.52
The qualified clarity of the qualified clarity of clarity clarity is qualified
The freeze-drying prods of prescription 1 and 3 is preferable, and the content after the lyophilizing is full, does not have atrophy, is loose block, color and luster homogeneous, and all easily dissolvings in 4ml water.Therefore, under the situation that obtains effect same,, select the excipient prescription of prescription 1, promptly use the raising agent and the cosolvent of mannitol (every bottle of 120mg) as this preparation as this preparation in order to save mannitol.
From this, the present invention is the most scientific and rational for the selection of adjuvant, technology.
The specific embodiment
Embodiments of the invention 1: get Radix Rhodiolae 600g and decoct with water 2 times,, adding 8 times of amounts of water for the first time, the time is 2 hours; Add 6 times of amounts of water for the 2nd time, the time is 1.5 hours, merges 2 times decocting liquid, filters, filtrate decompression is condensed into clear paste 1.30 (50 ℃), adds breviscapine (in lamp-dish flower acetic) 60g and sucrose 350g, dextrin 250g, and mixing is granulated, cross 12 mesh sieves, 60 ℃ of dryings, granulate, packing is promptly.Boiled water is taken after mixing it with water, 3 times on the one, one time 1 bag.
Embodiments of the invention 2: get Radix Rhodiolae 1400g and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste 1.20 (50 ℃), and spray drying adds breviscapine (in lamp-dish flower acetic) 20g and starch 55g, mixing, granulate, sieve drying, granulate, coating, packing, promptly.Boiled water is taken after mixing it with water, 3 times on the one, one time 2.Coating material preparation: get 1.8g polyacrylic resin and the abundant mixing of 95% ethanol 36ml, soak after 24 hours, filter, promptly.
Embodiments of the invention 3: get Radix Rhodiolae 600g and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste 1.15 (50 ℃),, spray drying, add breviscapine (in lamp-dish flower acetic) 20g and micropowder silica gel 24g, mixing is granulated, sieve drying, granulate, add carboxymethyl starch sodium 1.1g and magnesium stearate 0.5g, mixing, tabletting, the bag film-coat, promptly.Use mixing in water for oral taking, 3 times on the one, one time 1.
Coating material preparation: get the 9g polyacrylic resin, add 95% ethanol 170ml, soaks 24 hours to all dissolvings, other gets 1.5gPEG-6000 and adds a small amount of hot water and make it dissolving, in the resin solution, stirs evenly in the adding, and filtration gets final product.
Embodiments of the invention 4: get Radix Rhodiolae 1400g, be ground into coarse powder, add 12 times of amount 60% ethanol percolations, percolate reclaims ethanol, is concentrated into to add 6 times of water gagings behind 1.2 (60 ℃) and boil dissolving, filter, filtrate is concentrated into 1.1 (60 ℃) back with water saturated equal-volume sec-butyl alcohol extraction 3 times, the reclaim under reduced pressure sec-butyl alcohol, and filtrate is concentrated into dried, pulverize for fine powder, with breviscapine (in lamp-dish flower acetic) 60g mixing; Other gets PEG-6000 after being heated to fusion in the water-bath, adds said mixture, stirs evenly, and 80-90 ℃ of insulation dissolved in the cold liquid paraffin, and inhale and remove surface liquid paraffin, drying, promptly.Oral, 3 times on the one, one time 12 ball.
Embodiments of the invention 5: get Radix Rhodiolae 1000g, be ground into coarse powder, add 12 times of amount 65% ethanol percolations, percolate reclaims ethanol, add the water boil dissolving after concentrating, filter, filtrate concentrates the back with water saturated equal-volume sec-butyl alcohol extraction 3 times, the reclaim under reduced pressure sec-butyl alcohol, ethanol with the speed eluting of 65% ethanol with per minute 3ml, is reclaimed in the concentrated back of filtrate on polyamide chromatography post, add 5 times of water gagings after eluent concentrates and boil, filtrate is condensed into the dense clear paste that every 1ml is equivalent to medical material 10g, in order to preparation injection, glucose infusion liquid, freeze-dried powder.
The injection preparation: the rhodioside extract adds 1000ml water for injection and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boils, and filters, and filtrate is regulated about pH to 6.5 with citric acid soln, filters clear and bright; Breviscapine (in lamp-dish flower acetic) 40g adds 1000ml water for injection and stirs evenly, regulate about pH to 7.5 with sodium hydroxide solution, filter clear and brightly, filtrate is mixed with above-mentioned Radix Rhodiolae extract solution, 80 ℃ of heating, activated carbon adsorption 10 minutes, add water to 5000ml, regulate about pH to 6.5, filter, embedding is in the bent neck ampoule of 5ml, promptly.1 5-10ml 1 time on the 1st, faces with preceding adding 100-200ml5% or 10% glucose injection iv drip.
Glucose infusion liquid prepares: Radix Rhodiolae extract adds 2000ml water for injection and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boils, and filters, and filtrate is regulated about pH to 6.5 with citric acid soln, filters, and gets Radix Rhodiolae extract solution; Breviscapine (in lamp-dish flower acetic) 40g adds 5000ml water for injection and stirs evenly, and regulates about pH to 7.5 with sodium hydroxide solution, filters, filtrate and above-mentioned Radix Rhodiolae extract solution merge, and regulate about pH6.5 80 ℃ of heating, filtrate for later use is filtered in activated carbon adsorption 10 minutes; After getting the 5000g glucose and adding 30000 waters for injection and boil dissolving, activated carbon adsorption 15 minutes, filtering decarbonization pumps into rare joining in the cylinder after clear and bright, adds above-mentioned Radix Rhodiolae extract and breviscapine filtrate, add water to 100000ml, regulate about pH to 5.3, filter clear and brightly, embedding is in the 100ml infusion bottle, sterilization, promptly.1 100-200ml, intravenous drip, 1 is once.
The freeze-dried powder preparation:
Radix Rhodiolae extract adds 300ml water for injection and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boils, and filters, and filtrate is regulated about pH to 6.5 with citric acid soln, filters, and gets Radix Rhodiolae extract solution; Breviscapine (in lamp-dish flower acetic) 40g adds 300ml water for injection and stirs evenly, and regulates about pH to 7.5 with sodium hydroxide solution, filters, filtrate and above-mentioned Radix Rhodiolae extract solution merge, and regulate about pH6.5 70-80 ℃ of heating, filtrate for later use is filtered in activated carbon adsorption; Get mannitol 120g and add 600ml water for injection and boil dissolving, activated carbon adsorption 15 minutes, filtering decarbonization adds the above-mentioned mixed liquor of handling well, add the injection water to 2000ml, regulate about pH to 6.5, filters clear and brightly, under aseptic condition, press every bottle of 2ml packing, lyophilization is sealed, promptly.1 1-2 bottle, faces with dissolving in 5% or 10% glucose injection of preceding adding 100ml and dilution back and uses at every day 1 time.
Table 1: this injection is to the influence of experimental dog cerebral ischemia (x ± SD)
Dosage * full brain of number of times dog number heavily the heavy ischemic region in cerebral ischemia district heavy/full brain is heavy
Group
((g) (g) (%) for mg/kg * c) (only)
Matched group 5% glucose injection * 16 63.65 ± 5.40 18.90 ± 4.82 29.50 ± 6.32
SHUXUENING is annotated
0.75×1?????????????6????57.82±4.27????9.70±3.07**???????16.98±6.07**
Penetrate the liquid group
This injection
346.7×1????????????6????60.13±4.20????12.03±4.74*???????19.80±7.54*
Group
This injection
173.4×1????????????6????60.35±5.03????14.00±2.53*???????23.17±3.54*
Group
This injection
86.7×1?????????????6????60.47±4.44????15.87±3.55????????26.51±7.06
Group
The Radix Rhodiolae group
333.3×1????????????6????61.12±3.65????16.28±2.85????????26.63±4.29
Herba Erigerontis
13.3×1?????????????6????60.28±6.57????12.80±2.51*???????21.61±5.54*
Plain group
Annotate: each administration group and matched group be * P＜0.05 * * P＜0.01 relatively
Table 2: this injection is to the influence of dog blood flow of middle cerebral artery speed
Blood flow rate (cm/s, x ± SD)
Dosage * number of times dog number
15min after the administration before the group administration
(mg/kg * c) (only)
Peak velocity mean flow rate peak velocity mean flow rate
20.58??????9.70???????????21.38??????9.70
Matched group 5% glucose injection * 16
±4.81????±1.02??????????±5.01????±3.01
SHUXUENING is annotated 21.45 12.43 27.02 17.38**
0.75mg×1???????????6
Penetrate agent group ± 6.94 ± 5.05 ± 8.51 ± 5.13
This injection 24.47 13.43 31.05* 20.27**
346.7×1????????????6
Group ± 5.47 ± 5.10 ± 7.35 ± 6.20
This injection 21.57 11.72 26.82 14.98
173.4×1????????????6
Group ± 10.05 ± 6.44 ± 16.46 ± 9.37
This injection 17.95 9.83 20.87 11.75
86.7×1?????????????6
Group ± 9.42 ± 4.67 ± 12.47 ± 6.43
19.98?????10.30???????????24.85?????12.05
Radix Rhodiolae group 333.3 * 16
±7.33????±3.84??????????±9.12????±4.28
Herba Erigerontis 20.48 11.83 30.75* 15.80*
13.3×1?????????????6
Plain group ± 7.52 ± 4.60 ± 7.48 ± 6.09
Annotate: each administration group and matched group be * P＜0.05 * * P＜0.01 relatively
The influence that this injection of table 3 is tested mice head-breaking global brain ischemia (X ± SD)
Dosage * number of times Mus number number of times of breathing of dehiscing
Group
((only) (inferior) of mg/kg * c)
Model group 5% glucose injection * 5 10 8.70 ± 2.63
SHUXUENING ZHUSHEYE group 1.5 * 5 10 11.60 ± 2.17**
This injection group 693.4 * 5 10 12.40 ± 2.63**
This injection group 346.7 * 5 10 11.40 ± 2.32*
This injection group 173.4 * 5 10 10.00 ± 1.83
Radix Rhodiolae group 666.7 * 5 10 10.90 ± 0.97*
Breviscapine group 26.6 * 5 10 11.10 ± 3.11
Annotate: administration group and model group be * p＜0.05 * * p＜0.01 relatively
The influence of table 4 pair anesthetized dog ligation LAD myocardial ischemia zymetology index and left ventricle infarction size (X ± SD, N=6)
| Group | Dosage (mg/kg) | ????LDH(U/L) | ????CPK(U/L) | Left side chamber infarction size (%) | ||
| Before the ligation | After the ligation | Before the ligation | After the ligation | |||
| 5% glucose group SHUXUENING ZHUSHEYE group red light injection group Radix Rhodiolae group breviscapine group | 5% glucose injection 0.75 346.7 173.4 86.70 333.3 13.3 | ??43.00± ????16.80 ??48.83±13.48 ??46.83±16.34 ??46.83±1.60 ??44.83±13.57 ??49.50±24.53 ??43.33±20.23 | ??335.50±106.27 ??114.00±19.65** ??121.33±18.21** ??257.00±55.54 ??329.33±105.32 ??256.67±68.58 ??139.33±18.51** | ??64.17±13.57 ??82.00±17.65 ??97.67±49.73 ??71.00±21.68 ??69.83±15.59 ??75.50±18.51 ??66.83±11.84 | 307.17±63.01 139.67±19.53** 204.33±40.71** 218.67±54.80* 264.33±153.32 202.00±50.88** 175.50±63.59** | ??15.70±2.15 ??11.04±2.01** ??11.76±1.83** ??12.85±2.12* ??13.56±3.81 ??13.20±1.81* ??11.61±3.15* |
Annotate: each administration group and 5% glucose group be * P＜0.05 * * P＜0.01 relatively
The influence of the heart rate of table 5 pair anesthetized dog ligation LAD myocardial infarction and ischemia model (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Ligation LAD increases and decreases ratio | |
| Before the medicine | 15min behind the medicine | ????5min??????10min??????15min?????30min?????60min?????120min | |||
| ????HR (beat/min) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ??-- ??0.75 ??346.7 ??173.4 ??86.7 ??333.3 ??13.3 | ????158.00 ????±18.71 ????183.83 ????±17.13 ????186.00 ????±38.75 ????197.67 ????±14.45 ????175.50 ????±31.03 ????168.00 ????±29.11 ????211.50 ????±17.80 | ????171.67 ????±26.82 ????70.90 ????16.14± ????171.33 ????±38.89 ????191.50 ????±15.88 ????168.67 ????±29.23 ????166.83 ????±29.07 ????206.17 ????±10.85 | ????0.03??????0.01???????-0.05?????-0.04?????-0.05?????-0.11 ????±0.13????±0.11?????±0.14????±0.16????±0.12????±0.16 ????-0.08?????-0.09??????-0.09?????-0.10?????-0.15?????-0.19 ????±0.14????±0.11?????±0.17????±0.19????±0.17????±0.17 ????-0.07?????-0.16??????-0.12?????-0.13?????-0.19?????-0.21 ????±0.07????±0.09?????±0.09????±0.10????±0.10????±0.14 ????-0.07?????-0.10??????-0.09?????-0.13?????-0.20?????-0.18 ????±0.04????±0.07?????±0.07????±0.07????0.09±????????????±0.08 ????-0.05?????-0.07??????-0.11?????-0.14?????-0.17??????-0.16 ????±0.14????±0.12?????±0.14????±0.13????±0.14????±0.13 ????-0.10?????-0.12??????-0.14?????-0.14?????-0.16?????-0.17 ????±0.09????±0.10?????±0.09????±0.06????±0.06????±0.06 ????-0.07?????-0.12??????-0.12?????-0.13?????-0.15?????-0.15 ????±0.07????±0.07?????±0.07????±0.09????±0.09????±0.11 |
Annotate: each administration group and 5% glucose group be P＞0.05 relatively
The influence of the average femoral artery pressure of table 6 pair anesthetized dog ligation LAD myocardial infarction and ischemia model (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Increase and decrease ratio behind the ligation LAD | |
| Before the medicine | 15min behind the medicine | ????5min??????10min?????15min?????30min?????60min?????120min | |||
| ????MAP ??(mmHG) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ??-- ??0.75 ??346.7 ??173.4 ??86.7 ??333.3 ??13.3 | ??79.28 ??±38.58 ??104.56 ??±19.48 ??105.22 ??±22.78 ??106.39 ??±16.07 ??92.72 ??±26.18 ??110.17 ??±21.08 ??105.28 ??±17.65 | ????78.89 ????±40.26 ????98.06 ????±17.27 ????103.56 ????±22.08 ????106.06 ????±16.21 ????92.06 ????±19.17 ????94.83 ????±13.84 ????106.89 ????±10.50 | ????-0.08?????-0.06?????-0.16?????-0.23?????-0.26?????-0.29 ????±0.26????±0.32????±0.23????±0.22????±0.30????±0.30 ????-0.17?????-0.18?????-0.21?????-0.21?????-0.28?????-0.32 ????±0.11????±0.11????±0.13????±0.14????±0.25????±0.22 ????-0.05?????-0.04?????-0.06?????-0.09?????-0.10?????-0.21 ????±0.06????±0.06????±0.06????±0.07????±0.12????±0.12 ????-0.11?????-0.14?????-0.10?????-0.14?????-0.14?????-0.20 ????±0.11????±0.11????±0.08????±0.13????±0.17????±0.16 ????-0.03?????-0.04?????-0.10?????-0.10?????-0.13?????-0.15 ????±0.18????±0.16????±0.14????±0.12????±0.12????±0.12 ????-0.10?????-0.1?1????-0.13?????-0.17?????-0.23?????-0.25 ????±0.09????±0.08????±0.08????±0.06????±0.09????±0.10 ????-0.08?????-0.10?????-0.12?????-0.12?????-0.15?????-0.15 ????±0.07????±0.09????±0.09????±0.09????±0.13????±0.23 |
Annotate: each administration group and 5% glucose group be P＞0.05 relatively
The influence of the epicardial electrogram of table 7 pair anesthetized dog ligation LAD myocardial infarction and ischemia model (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Increase and decrease ratio behind the ligation LAD | |
| Before the medicine | 15min behind the medicine | ????5min??????10min?????15min?????30min?????60min?????120min | |||
| ??E piECC ST displacement (mv) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ????-- ????0.75 ????346.7 ????173.4 ????86.7 ????333.3 ????13.3 | ????0.09 ????±0.05 ????0.11 ????±0.04 ????0.13 ????±0.04 ????0.16 ????±0.09 ????0.11 ????±0.03 ????0.15 ????±0.08 ????0.10 ????±0.03 | ????0.10 ????±0.05 ????0.11 ????±0.55 ????0.12 ????±0.04 ????0.15 ????±0.08 ????0.11 ????±0.04 ????0.14 ????±0.07 ????0.11 ????±0.04 | ????0.71??????0.88??????0.17??????0.88??????0.30??????0.79 ????±2.01????±1.81????±0.24????±1.00????±1.04????±2.18 ????-0.08*????0.12**????-0.04?????0.01??????0.08*?????0.10 ????±0.34????±0.22????±0.20????±0.30????±0.30????±0.84 ????0.02*?????0.20*?????0.26??????0.07??????0.46??????0.29 ????±0.20????±0.10????±0.26????±0.15????±0.24????±0.14 ????0.32??????0.41??????0.17??????0.16??????0.13??????0.28 ????±0.55????±0.70????±0.31????±0.24????±0.41????±0.37 ????0.30??????0.38??????0.52??????0.54??????0.72??????0.77 ????±0.15????±0.17????±0.29????±0.28????±0.25????±0.62 ????0.13*?????0.14*?????0.51??????0.42??????0.44??????0.73 ????±0.20????±0.44????±1.00????±0.79????±0.54????±1.44 ????0.23??????0.33*?????0.16??????0.42??????0.35??????0.49 ????±0.27????0.28±??????????±0.46?????±0.43????±0.41????±0.69 |
Annotate: each administration group and 5% glucose group be * P＜0.05 * * P＜0.01 relatively
The table 8 pair kinemic influence of anesthetized dog ligation LAD myocardial infarction and ischemia model (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Increase and decrease ratio behind the ligation LAD | |
| Before the medicine | 15min behind the medicine | ????5min?????10min?????15min?????30min?????60min?????120min | |||
| ????CO ??(L/min) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ????-- ????0.75 ????346.7 ????173.4 ????86.7 ????333.3 ????13.3 | ??2.17 ??±0.31 ??2.28 ??±0.14 ??2.12 ??±0.23 ??2.24 ??±0.25 ??2.08 ??±0.30 ??2.01 ??±0.31 ??2.05 ??±0.30 | ????2.21 ????±0.25 ????2.21 ????±0.14 ????1.93 ????±0.24 ????1.93 ????±0.23 ????1.88 ????±0.33 ????1.83 ????±0.32 ????1.92 ????±0.37 | ????-0.10????-0.15?????-0.08?????-0.02?????-0.16?????-0.15 ????±0.13???±0.13????±0.22????±0.27????±0.19????±0.16 ????-0.12????-0.14?????-0.09?????-0.17?????-0.13?????-0.15 ????±0.09???±0.08????±0.16????±0.13????±0.13????±0.13 ????-0.08????-0.18?????-0.15?????-0.27?????-0.29?????-0.27 ????±0.08???±0.05????±0.06????±0.07????±0.03????±0.11 ????-0.07????-0.21?????-0.26?????-0.31?????-0.43?????-0.40 ????±0.03???±0.04????±0.06????±0.09????±0.06????±0.06 ????-0.15????-0.24?????-0.32?????-0.26?????-0.26?????-0.24 ????±0.17???±0.16????±0.15????±0.15????±0.12????±0.14 ????-0.11????-0.19?????-0.22?????-0.23?????-0.13?????-0.27 ????±0.10???±0.05????±0.08????±0.08????±0.07????±0.10 ????-0.13????-0.19?????-0.28?????-0.18?????-0.21?????-0.20 ????±0.05???±0.07????±0.06????±0.09????±0.14????±0.16 |
Annotate: each administration group and 5% glucose group be P＞0.05 relatively
Table 9 red light injection to the influence of anesthetized dog ligation LAD myocardial ischemia LV+dp/dt (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Ligation LAD increases and decreases ratio | |
| Before the medicine | 15min behind the medicine | ????5min??????10min?????15min?????30min?????60min?????120min | |||
| ??LV+dp/dt ??(mmHg/sec) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ????-- ????0.75 ????346.7 ????173.4 ????86.7 ????333.3 ????13.3 | ????2112.83 ????± ????????751.45 ????1581.33 ????± ????????419.65 ????1615.33 ????± ????????415.79 ????1433.67 ????± ????????534.45 ????1327.33 ????± ????????541.79 ????1865.33 ????± ????????947.44 ????2120.83 ????± ???????560.66 | ????1621.00 ????±375.91 ????1471.33 ????±181.33 ????1488.50 ????±325.83 ????1370.50 ????±602.59 ????1099.83 ????±456.62 ????1620.17 ????±594.92 ????1930.83 ????±279.18 | ????-0.36?????-0.29?????-0.45?????-0.33?????-0.37?????-0.50 ????±0.13????±0.45????±0.15????±0.42????±0.23????±0.21 ????-0.17*????-0.14?????-0.35?????-0.25?????-0.30?????-0.34 ????±0.18????±0.09????±0.20????±0.27????±0.24????±0.12 ????0.02**????-0.01*????-0.08**???-0.04?????-0.11?????-0.21 ????±0.14????±0.13????±0.14????±0.15????±0.19????±0.31 ????0.11??????-0.07?????-0.02?????-0.09?????0.02??????-0.14 ????±0.65????±0.51????±0.55????±0.41????±0.51????±0.49 ????0.12*?????0.07??????0.02*?????0.07??????-0.05?????-0.09* ????±0.48????±0.37????±0.41????±0.35????±0.42????±0.29 ????-0.24?????-0.17?????-0.18?????-0.29?????-0.29?????-0.29 ????±0.29????±0.38????±0.34????±0.25????±0.34????±0.28 ????-0.20?????-0.22?????-0.20?????-0.27?????-0.29?????-0.33 ????±0.19????±0.22????±0.25????±0.26????±0.24????±0.15 |
Annotate: each administration group and 5% glucose group be * P＜0.05 relatively, * * P＜0.01
Table 10 red light injection to the influence of anesthetized dog ligation LAD myocardial ischemia LV-dp/dt (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Ligation LAD increases and decreases ratio | |
| Before the medicine | 15min behind the medicine | ????5min??????10min?????15min?????30min?????60min?????120min | |||
| ?LV-dp/dt (mmHg/sec) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ??-- ??0.75 ??346.7 ??173.4 ??86.7 ??333.3 ??13.3 | ??1783.17 ????± ????796.19 ??1581.33 ????± ????419.65 ??1424.50 ????± ????480.05 ??1249.17 ????± ????221.26 ??1272.00 ????± ????504.15 ??1503.17 ????± ????301.90 ??1751.83 ????± ????222.10 | ????1230.50 ????±446.25 ????1471.33 ????±181.33 ????1331.17 ????±313.04 ????1206.50 ????±174.55 ????1135.00 ????±319.23 ????1314.00 ????±303.62 ????1545.83 ????±326.84 | ????-0.36?????-0.33?????-0.44?????-0.27?????-0.36?????-0.50 ????±0.21????±0.37????±0.27????±0.56????±0.27????±0.30 ????-0.30?????-0.17?????-0.38?????-0.28?????-0.30?????-0.58 ????±0.17????±0.17????±0.19????±0.27????±0.30????±0.46 ????-0.05*????0.00??????-0.14*????0.01??????-0.07?????-0.19 ????±0.22????±0.20????±0.13????±0.16????±0.37????±0.50 ????-0.01*????0.16??????-0.15?????-0.26?????-0.22?????-0.26 ????±0.30????±0.30????±0.26????±0.23????±0.28????±0.19 ????-0.14?????-0.15?????-0.14?????-0.13?????-0.17?????-0.23 ????±0.39????±0.32????±0.33????±0.32????±0.37????±0.30 ????-0.25?????-0.29?????-0.26?????-0.32?????-0.38?????-0.42 ????±0.28????±0.21????±0.22????±0.25????±0.30????±0.21 ????-0.19?????-0.27?????-0.26?????-0.32?????-0.36?????-0.45 ????±0.08????±0.08????±0.14????±0.18????±0.13????±0.07 |
Annotate: each administration group and 5% glucose group be * P＜0.05 relatively,
Table 11 red light injection to the influence of anesthetized dog ligation LAD myocardial infarction and ischemia model LVP (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Increase and decrease ratio behind the ligation LAD | |
| Before the medicine | 15min behind the medicine | ????5min??????10min?????15min?????30min?????60min?????120min | |||
| ??LVP (mmHg) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ????-- ????0.75 ????346.7 ????173.4 ????86.7 ????333.3 ????13.3 | ????60.30 ????±15.50 ????70.90 ????±16.14 ????67.30 ????±12.52 ????63.60 ????±13.41 ????55.40 ????±17.65 ????76.63 ????±9.95 ????78.90 ????±10.79 | ????57.18 ??±13.35 ????68.00 ??±14.55 ????60.83 ??±7.17 ????61.93 ??±15.72 ????49.90 ??±13.77 ????70.43 ??±15.26 ????67.87 ??±11.47 | ????-0.06?????-0.18?????-0.20?????-0.23?????-0.24?????-0.27 ????±0.16????±0.13????±0.13????±0.14????±0.20????±0.13 ????-0.19?????-0.20?????-0.30?????-0.30?????-0.34?????-0.35 ????±0.22????±0.19????±0.17????±0.21????±0.16????±0.13 ????-0.05?????-0.03?????-0.04*????-0.03**????-0.05????-0.15 ????±0.18????±0.11????±0.09????±0.07????±0.14????±0.24 ????-0.02?????-0.12?????-0.11?????-0.16?????-0.14?????-0.12 ????±0.28????±0.29????±0.27????±0.24????±0.25????±0.15 ????-0.05?????-0.05?????-0.06?????-0.07?????-0.09?????-0.10 ????±0.36????±0.30????±0.30????±0.26????±0.31????±0.22 ????-0.19?????-0.16?????-0.19?????-0.23?????-0.30?????-0.35 ????±0.23????±0.23????±0.20????±0.18????±0.25????±0.15 ????-0.26*????-0.27?????-0.30?????-0.33?????-0.43?????-0.37 ????±0.13????±0.18????±0.21????±0.20????±0.25????±0.37 |
Annotate: each administration group and 5% glucose group be * P＜0.05 relatively, * * P＜0.01
Table 12 red light injection to the influence of anesthetized dog ligation LAD myocardial infarction and ischemia model LVEDP (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Increase and decrease ratio behind the ligation LAD | |
| Before the medicine | 15min behind the medicine | ????5min????10min?????15min?????30min?????60min?????120min | |||
| ??LVEDP ??(mmHg) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ????-- ????0.75 ????346.7 ????173.4 ????86.7 ????333.3 ????13.3 | ????3.62 ????±1.67 ????4.25 ????±1.48 ????3.12 ????±1.55 ????3.20 ????±1.04 ????3.48 ????±1.96 ????4.78 ????±1.27 ????4.53 ????±1.85 | ????3.05 ????±2.05 ????4.13 ????±1.11 ????3.43 ????±2.17 ????3.40 ????±0.86 ????3.37 ????±1.62 ????4.42 ????±1.32 ????4.02 ????±1.41 | ????0.75????-0.02?????0.02??????0.10??????1.07??????0.56 ????±1.66??±0.78????±0.78????±0.85????±1.88????±0.86 ????0.29????0.26??????0.55??????0.13??????0.09??????0.42 ????±0.57??±0.51????±1.03????±0.28????±0.35????±0.98 ????-0.17???-0.13?????-0.04?????-0.22?????-0.20?????0.25 ????±0.46??±0.32????±0.28????±0.22????±0.21????±0.37 ????0.14????0.13??????0.26??????0.14??????0.22??????-0.14 ????±0.20??±0.15????±0.32????±0.29????±0.47????±0.49 ????0.09????0.06??????0.09??????-0.02?????0.12??????0.58 ????±0.41??±0.32????±0.29????±0.27????±0.43????±0.82 ????-0.08???-0.14??????-0.01????-0.05?????-0.01?????0.39 ????±0.25??±0.23????±0.24????±0.18????±0.17????±0.19 ????-0.14???-0.21?????-0.15?????-0.19?????-0.03?????0.19 ????±0.42??±0.42????±0.37????±0.48????±0.70????±0.69 |
Annotate: each administration group and 5% glucose group be * P＜0.05 relatively
Table 13 red light injection to the influence of anesthetized dog ligation LAD myocardial ischemia oxygen consumption index (X ± SD, n=6)
| Index | Group | Dosage (mg/kg) | Contrast | Increase and decrease ratio behind the ligation LAD | |
| Before the medicine | 15min behind the medicine | ????5min??????10min??????15min?????30min?????60min?????120min | |||
| ?????MVO 2???(mlO 2/ ??min/100g) | 5% glucose group Shu Xuening injection group red light parenteral solution rhodiola root group Breviscapinun group | ????-- ????0.75 ????346.7 ????173.4 ????86.7 ????333.3 ????13.3 | ??12.64 ??±4.65 ??17.43 ??±2.85 ??17.29 ??±3.22 ??18.85 ??±2.29 ??15.31 ??±4.51 ??16.04 ??±3.34 ??18.76 ??±2.99 | ????13.29 ????±4.62 ????15.09 ????±2.14 ????15.81 ????±3.04 ????17.59 ????±2.17 ????13.96 ????±2.85 ????14.07 ????±2.62 ????18.16 ????±1.75 | ????-0.03?????-0.01??????-0.10?????-0.14?????-0.18?????-0.26 ????±0.07????±0.13?????±0.10????±0.14????±0.25????±0.22 ????-0.22*????-0.21*?????-0.22?????-0.26?????-0.32?????-0.37 ????±0.16????±0.16?????±0.24????±0.23????±0.28????±0.21 ????-0.09?????-0.17**????-0.16*????-0.26*????-0.28?????-0.34 ????±0.07????±0.03?????±0.04????±0.05????±0.08????±0.12 ????-0.14?????-0.20**????-0.20?????-0.25?????-0.33?????-0.36 ????±0.12????0.09±????????????±0.09?????±0.10????±0.14????±0.13 ????-0.11?????-0.14??????-0.21?????-0.25?????-0.31?????-0.35 ????±0.16????±0.13?????±0.16????±0.12????±0.12????±0.10 ????-0.16*????-0.19*?????-0.23*????-0.29*????-0.38?????-0.40 ????±0.11????±0.11?????±0.08????±0.06????±0.05????±0.08 ????-0.13?????-0.18*?????-0.22?????-0.25?????-0.28?????-0.28 ????±0.12????±0.14?????±0.13????±0.14????±0.16????±0.25 |
Annotate: compare * P＜0.05 * * P＜0.01 with 5% glucose group
Table 14 red light injection is to the influence of the open number of Mice Auricle point of intersect of the capillary network (x ± SD)
| Group | Dosage (mg/kg) | Mus number (only) | The open number (individual/visual field) in auricular microcirculation blood capillary site | ||||
| Before the injection Adr | 1min behind the injection Adr | 5min behind the injection Adr | 10min behind the injection Adr | 15min behind the injection Adr | |||
| The high Radix Rhodiolae group of matched group model group SHUXUENING ZHUSHEYE group red light injection breviscapine group | ????-- ????-- ????1.5 ????693.3 ????346.7 ????173.4 ????666.6 ????26.6 | ????10 ????10 ????10 ????10 ????10 ????10 ????10 ????10 | ??18.2±2.66 ??19.7±3.13 ??20.2±1.81 ??22.1±2.60 ??21.8±2.97 ??21.3±3.40 ??20.8±2.97 ??19.4±2.63 | ??17.8±2.74 ??9.9±2.51 △△????14.1±2.64** ??12.4±1.90* ??12.3±1.49* ??10.5±1.35 ??12.9±1.20** ??14±1.49** | ??18.4±2.63 ??12.9±2.02 △△????17.5±1.90** ??14.8±1.32* ??15±1.56* ??13.4±2.12 ??16.1±1.29** ??16.6±0.97** | ????18±2.40 ????15.7±2.50 △????????19.5±1.65** ????20.4±1.71** ????18.5±2.12* ????18.5±2.2* ????18.8±1.93** ????17.9±1.91* | ??17.9±2.33 ??18.4±1.43 ??19.5±1.65 ??20.4±1.71* ??18.5±2.12 ??19.3±1.94 ??19±2.45 ??17.9±1.91 |
Annotate: 1. model group and matched group compare △ P＜0.05 △ △ P＜0.01
2. each administration group and model group compare * P＜0.05 * * P＜0.01
Table 15 red light injection is to the influence of Mice Auricle microcirculation velocity of blood flow
| Group | Dosage (mg/kg) | Mus number (only) | The auricular microcirculation velocity of blood flow (μ m/s, x ± SD) |
| 15min behind the 10min injection Adr behind the 5min injection Adr behind the 1min injection Adr behind the injection Adr before the injection Adr | |||
| The high rhodiola root group of control group model group Shu Xuening injection group red light parenteral solution Breviscapinun group | ????-- ????-- ????1.5 ??693.3 ??346.7 ??173.4 ??666.6 ??26.6 | ??10 ??10 ??10 ??10 ??10 ??10 ??10 ??10 | ??705.7±46.76????706.5±40.95????????704.5±46.46??????707.2±42.87????????709.6±44.51 ??701.7±36.19????336.2±64.96 △△????????389.4±65.58 △△???468.5±60.75 △△????????596.0±41.31 △△????694.6±54.05????393.4±83.78????????467.3±81.62**????541.5±67.19*???????636.0±51.07 ??729.0±53.35????407.6±114.65???????485.4±66.68**????560.2±45.03**??????644.8±48.9* ??699.4±54.15????390.1±55.58????????503.2±412.2*?????563.6±44.76**??????650.6±48.50* ??681.1±43.94????381.0±56.04????????455.9±49.99*?????555.1±37.31**??????627.9±32.88 ??675.7±53.91????383.1±69.47????????446.5±55.4*??????540.5±51.96*???????635.1±58.1 ??673.4±59.64????377.2±49.2?????????448.2±43.58*?????536.1±41.09**??????633.6±40.07 |
Annotate: 1. model group and matched group compare △ P＜0.05 △ △ P＜0.01
2. each administration group and model group compare * P＜0.05 * * P＜0.01
Table 16 red light injection is to the influence of Mice Auricle microcirculation blood fluidised form
| Group | Dosage (mg/kg) | Mus number (only) | Auricular microcirculation blood fluidised form (divide, x ± SD) |
| 15min behind the 10min injection Adr behind the 5min injection Adr behind the 1min injection Adr behind the injection Adr before the injection Adr | |||
| The high Radix Rhodiolae group of matched group model group SHUXUENING ZHUSHEYE group red light injection breviscapine group | ????-- ????-- ????1.5 ????693.3 ????346.7 ????173.4 ????666.6 ????26.6 | ????10 ????10 ????10 ????10 ????10 ????10 ????10 ????10 | ????0.00±0.00????0.00±0.00??????0.00±0.00??????0.00±0.00?????0.00±0.00 ????0.00±0.00????2.80±0.42 △△???2.40±0.52 △△???1.50±0.71 △△??0.40±0.52 △????????0.00±0.00????2.00±0.00**????1.70±0.48**????1.00±0.00*????0.00±0.00* ????0.00±0.00????1.90±0.32**????1.80±0.42*?????1.00±0.00*????0.00±0.00* ????0.00±0.00????2.30±0.48*?????2.00±0.00*?????1.00±0.00*????0.20±0.42 ????0.00±0.00????2.70±0.48??????1.80±0.42*?????1.00±0.00*????0.30±0.48 ????0.00±0.00????1.70±0.48**????1.40±0.52**????1.00±0.00*????0.1±0.32 ????0.00±0.00????1.60±0.52**????1.20±0.42**????1.00±0.00*????0.00±0.00* |
Annotate: 1. model group and matched group compare △ P＜0.05 △ △ P＜0.01
2. each administration group and model group compare * P＜0.05 * * P＜0.01
Table 17 red light injection is to the influence of Mice Auricle microcirculation microcirculation third level arteries caliber
| Group | Dosage (mg/kg) | Mus number (only) | Auricular microcirculation third level arteries caliber (μ m, x ± SD) |
| 15min behind the 10min injection Adr behind the 5min injection Adr behind the 1min injection Adr behind the injection Adr before the injection Adr | |||
| The high Radix Rhodiolae group of matched group model group SHUXUENING ZHUSHEYE group red light injection breviscapine group | ????-- ????-- ????1.5 ????693.3 ????346.7 ????173.4 ????666.6 ????26.6 | ????10 ????10 ????10 ????10 ????10 ????10 ????10 ????10 | ????15.32±2.38????15.55±2.27??????15.48±2.00??????15.28±2.39??????15.41±2.38 ????16.78±1.47????10.40±2.07△△??11.13±1.51△△??12.98±0.71△????15.20±1.62 ????16.40±1.48????12.01±0.94*?????13.89±1.14**????14.71±0.77*?????15.51±1.52 ????16.33±1.18????13.02±0.73**????14.45±0.97**????15.18±0.81**????15.65±0.88* ????16.22±1.87????11.80±2.06??????13.15±1.58*?????15.2±0.91**?????15.46±0.76 ????17.10±1.33????12.44±2.19*?????13.80±1.55**????15.78±0.91**????16.14±0.85 ????16.69±1.30????12.98±1.61**????14.83±0.81**????14.83±0.82**????14.75±1.34 ????16.27±0.88????11.91±1.35??????13.04±1.16**????15.07±1.2**?????15.38±0.72 |
Annotate: 1. model group and matched group compare △ P＜0.05 △ △ P＜0.01 2. each administration group and model group comparison * P＜0.05 * * P＜0.01
Table 18 red light injection is to the influence of Mice Auricle microcirculation third level vein blood vessel caliber
| Group | Dosage (mg/kg) | Mus number (only) | Auricular microcirculation third level vein blood vessel caliber (μ m, x ± SD) |
| 15min behind the 10min injection Adr behind the 5min injection Adr behind the 1min injection Adr behind the injection Adr before the injection Adr | |||
| The high Radix Rhodiolae group of matched group model group SHUXUENING ZHUSHEYE group red light injection breviscapine group | ????-- ????-- ????1.5 ????693.3 ????346.7 ????173.4 ????666.6 ????26.6 | ????10 ????10 ????10 ????10 ????10 ????10 ????10 ????10 | ??22.24±1.51????21.96±1.54??????21.99±1.57??????22.08±1.39?????22.11±1.40 ??22.49±1.93????12.16±1.82 △△???14.20±1.89 △△????18.90±1.79 △△?19.58±1.60 △△????23.86±1.56????15.09±1.41**????16.74±1.36**????20.91±2.00*????21.89±1.66** ??22.28±1.37????15.01±1.04**????16.50±1.05**????20.40±0.83*????22.10±0.93** ??22.25±1.74????14.76±1.32**????16.79±1.27**????20.49±1.52*????22.10±1.43** ??22.58±2.01????14.67±0.77**????16.71±0.98**????20.21±0.78*????20.95±0.84* ??22.37±1.50????14.47±1.13**????15.57±0.74*?????20.64±1.00*????21.39±0.69** ??22.02±1.52????14.42±0.98**????16.93±0.91**????20.33±0.99*????20.98±0.77* |
Annotate: 1. 2. each administration group and model group comparison of model group and matched group comparison △ P＜0.05 △ △ P＜0.01
*P＜0.05
*P＜0.01
This injection of table 19 is to the dissolved influence of rabbit pulmonary thrombosis (X ± SD)
| Group | Drug dose (mg/kg) | Rabbit number (only) | Wet weight of thrombus (mg) | Thrombosis dry weight (mg) after the administration | |
| Before the administration | After the administration | ||||
| This injection of matched group urokinase group Radix Rhodiolae group breviscapine group | ??-- ??1000u ??693.3 ??346.7 ??173.4 ??666.6 ??26.6 | ????8 ????8 ????8 ????8 ????8 ????8 ????8 | ?300.49±1.37 ?299.89±1.25 ?299.94±1.46 ?299.86±1.16 ?299.48±1.45 ?300.15±1.27 ?300.33±0.98 | ?147.91±8.10 ?56.66±4.05** ?72.51±6.95** ?105.96±8.02** ?114.84±5.25** ?125.23±6.78** ?63.36±6.49** | ??47.58±4.36 ??18.51±2.09** ??20.21±4.60** ??30.45±4.47** ??33.60±5.07** ??35.49±4.98** ??21.71±4.27** |
Annotate: each administration group and 5% glucose injection group be * P＜0.05 relatively, * * P＜0.01
This injection of table 20 is to the influence of fibrinolysis time (X ± SD)
| Group | Dosage * sky (mg/kg * d) | Rabbit number (only) | Fibrinolysis time (min) |
| Blank this injection of group urokinase group Radix Rhodiolae group breviscapine group | ??????--- ????1000u×7 ????693.3×7 ????346.7×7 ????173.4×7 ????666.6×7 ????26.6×7 | ????8 ????8 ????8 ????8 ????8 ????8 ????8 | ????246.25±38.89 ????65.00±25.63*** ????131.25±62.21*** ????112.50±58.49*** ????107.50±55.493*** ????90.00±25.63*** ????112.50±41.32*** |
Annotate: each administration group and matched group are relatively
* *P＜0.001
This injection of table 21 is to the influence of deficiency of vital energy mice swimming time (resisting fatigue) (X ± SD)
| Group | Dosage * sky (mg/kg * d) | Mus number (only) | Swimming time (s) |
| Blank this injection of group model group ginseng aconite injection agent group group Radix Rhodiolae group breviscapine group | 5% glucose * 7 5% glucose * 7 6.67ml * 7 693.3 * 7 346.7 * 7 173.4 * 7 666.6 * 7 26.6 * 7 | ????10 ????10 ????10 ????10 ????10 ????10 ????10 ????10 | ????350.90±22.88 ????92.10±28.58△△△ ????????127.00±21.06** ????123.80±24.22** ????117.20±25.52* ????89.90±17.91 ????119.60±22.25* ????96.20±26.89 |
Annotate: 1. model group and normal control group comparison △ △ △ p＜0.001 2. administration group and matched group are relatively
*P＜0.05
*P＜0.01
This injection of table 22 is to the influence of deficiency of vital energy mice normal pressure resistant anoxia (x ± SD)
| Group | Dosage * sky (mg/kg * d) | Mus number (only) | Death time (min) | Rate elongation (%) |
| 5% this injection of glucose group model group ginseng aconite injection agent group group Radix Rhodiolae group breviscapine group | 5% glucose * 7 5% glucose * 7 6.67ml * 7 693.3 * 7 346.7 * 7 173.4 * 7 666.6 * 7 26.6 * 7 | ????10 ????10 ????10 ????10 ????10 ????10 ????10 ????10 | ????40.80±5.88 ????30.50±9.02△△△ ????????41.50±9.02** ????38.10±6.97** ????34.20±6.25 ????31.40±5.15 ????36.50±4.20** ????33.00±4.24 | ????- ????- ????36.07 ????24.92 ????12.13 ????2.95 ????19.67 ????8.20 |
Annotate: 1. model group and 5% glucose group comparison △ △ △ p＜0.001 2. administration group and model group are relatively
*P＜0.01
Claims (12)
1, be used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent: it mainly is prepared from by Radix Rhodiolae 600-1400 part and breviscapine (in lamp-dish flower acetic) 20-60 part.
2, according to the described Chinese medicine preparation that is used for the treatment of cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to components by weight percent: it is prepared from by 1000 parts of Radix Rhodiolaes and 40 parts of breviscapines (in lamp-dish flower acetic) and appropriate amount of auxiliary materials, and described adjuvant comprises according to the different dosage form of preparation: sucrose, dextrin, starch, polyacrylic resin, micropowder silica gel, carboxymethyl starch sodium, magnesium stearate, PEG-6000, mannitol.
3, according to claim 1 or the 2 described Chinese medicine preparation that are used for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that: described preparation comprises granule, hard capsule, soft capsule, tablet, drop pill, oral liquid, injection, comprise: injection, glucose infusion liquid, freeze-dried powder, slow releasing preparation, controlled release preparation etc.
4, as claim 1, the 2 or 3 described preparation methoies that are used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease, it is characterized in that: after Radix Rhodiolae being adopted the method effective component extracting of decocting in water or percolation, add breviscapine again and suitable adjuvant is prepared into different preparations.
5, according to the described preparation method that is used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: granule can prepare like this: get Radix Rhodiolae and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste, add breviscapine and sucrose, dextrin, mixing is granulated, sieve, drying, granulate, packing is promptly.
6, according to the described preparation method that is used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: capsule can prepare like this: get Radix Rhodiolae and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste, spray drying, add breviscapine and starch, mixing is granulated, sieve, drying, granulate, coating, packing, that is, wherein coating material can prepare like this: get 1.8g polyacrylic resin and the abundant mixing of 95% ethanol 36ml, soak after 24 hours, filter, promptly.
7, according to the described preparation method that is used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: tablet can prepare like this: get Radix Rhodiolae and decoct with water 2 times, merge 2 times decocting liquid, filter, filtrate decompression is condensed into clear paste, and spray drying adds breviscapine and micropowder silica gel, mixing, granulate, sieve drying, granulate, add carboxymethyl starch sodium and magnesium stearate, mixing, tabletting, the bag film-coat, that is, wherein coating material can prepare like this: get the 9g polyacrylic resin, add 95% ethanol 170ml, soak 24 hours to all dissolvings, other get 1.5gPEG-6000 add a small amount of hot water make it the dissolving, in the resin solution, stir evenly in the adding, filter, get final product.
8, according to the described preparation method that is used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: drop pill can prepare like this: get Radix Rhodiolae, be ground into coarse powder, add ethanol percolation, percolate reclaims ethanol, add the water boil dissolving after concentrating, filter, filtrate concentrates the back with water saturated equal-volume sec-butyl alcohol extraction 3 times, the reclaim under reduced pressure sec-butyl alcohol, filtrate is concentrated into dried, pulverizes to be fine powder, with the breviscapine mixing; Other gets PEG-6000 after being heated to fusion in the water-bath, adds said mixture, stirs evenly, and 80-90 ℃ of insulation dissolved in the cold liquid paraffin, and inhale and remove surface liquid paraffin, drying, promptly.
9, according to the described preparation method that is used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: injection can prepare like this: get Radix Rhodiolae, be ground into coarse powder, add ethanol percolation, percolate reclaims ethanol, add the water boil dissolving after concentrating, filter, filtrate concentrates the back with water saturated equal-volume sec-butyl alcohol extraction 3 times, the reclaim under reduced pressure sec-butyl alcohol, filtrate concentrate the back on polyamide chromatography post with ethanol elution, reclaim ethanol, add water boil after eluent concentrates, filtrate is condensed into dense clear paste, adds breviscapine again and suitable adjuvant prepares injection, glucose infusion liquid, freeze-dried powder.
10, according to claim 4 or the 9 described preparation methoies that are used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease, it is characterized in that: injection can prepare like this: Radix Rhodiolae extract adds the injection water and stirs evenly, and regulates about pH to 9.0 with sodium hydroxide solution, boil, filter, filtrate is regulated pH to about 7.5 with the broad liquid of citric acid, filter clear and bright, filtrate is mixed with above-mentioned Radix Rhodiolae extract solution, heating, activated carbon adsorption, regulate about pH to 6.5, filter, embedding, promptly.
11, according to claim 4 or the 9 described preparation methoies that are used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease, it is characterized in that: glucose infusion liquid can prepare like this: Radix Rhodiolae extract adds the injection water and stirs evenly, regulate about pH to 9.0 with sodium hydroxide solution, boil, filter, filtrate is regulated about pH to 6.5 with citric acid soln, filters, and gets Radix Rhodiolae extract solution; Breviscapine adds the injection water and stirs evenly, and regulates about pH to 7.5 with sodium hydroxide solution, filters, and filtrate and Radix Rhodiolae extract solution merge, regulate about pH6.5, and heating, filtrate for later use is filtered in activated carbon adsorption; After getting glucose and adding injection water boils dissolving, activated carbon adsorption, filtering decarbonization pumps into rare joining in the cylinder after clear and bright, adds above-mentioned Radix Rhodiolae extract and breviscapine filtrate, adds water to full dose, regulates about pH to 5.3, filters clear and brightly, and embedding is sterilized, promptly.
12, according to claim 4 or the 9 described preparation methoies that are used for the treatment of the Chinese medicine preparation of cardiovascular and cerebrovascular disease, it is characterized in that: freeze-dried powder can prepare like this: Radix Rhodiolae extract adds the injection water and stirs evenly, regulate about pH to 9.0 with sodium hydroxide solution, boil, filter, filtrate is regulated about pH to 6.5 with citric acid soln, filters, and gets Radix Rhodiolae extract solution; Breviscapine adds the injection water and stirs evenly, and regulates about pH to 7.5 with sodium hydroxide solution, filters, and filtrate and Radix Rhodiolae extract solution merge, regulate about pH6.5, and heating, filtrate for later use is filtered in activated carbon adsorption; Get mannitol and add the injection water and boil dissolving, activated carbon adsorption, filtering decarbonization adds the above-mentioned mixed liquor of handling well, adds water to full dose, about adjusting pH to 6.5, filters clear and brightly, aseptic subpackaged, and lyophilization is sealed, promptly.
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| CN 200410022445 CN1275609C (en) | 2004-04-29 | 2004-04-29 | Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process |
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| CN 200410022445 CN1275609C (en) | 2004-04-29 | 2004-04-29 | Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process |
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| CN1275609C CN1275609C (en) | 2006-09-20 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893196A (en) * | 2014-04-02 | 2014-07-02 | 闫莹 | Medical application of sedoisoprosan and pharmaceutical composition of sedoisoprosan |
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| CN101181333B (en) * | 2007-11-22 | 2010-12-29 | 陕西步长制药有限公司 | Chinese medicine injection for curing cardiovascular and cerebrovascular diseases as well as method for manufacture and detection thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893196A (en) * | 2014-04-02 | 2014-07-02 | 闫莹 | Medical application of sedoisoprosan and pharmaceutical composition of sedoisoprosan |
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