CN101062027B - Taurine and medical combination for treating cardiovascular and cerebrovascular diseases - Google Patents

Taurine and medical combination for treating cardiovascular and cerebrovascular diseases Download PDF

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CN101062027B
CN101062027B CN2006100438986A CN200610043898A CN101062027B CN 101062027 B CN101062027 B CN 101062027B CN 2006100438986 A CN2006100438986 A CN 2006100438986A CN 200610043898 A CN200610043898 A CN 200610043898A CN 101062027 B CN101062027 B CN 101062027B
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cattle
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CN101062027A (en
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黄振华
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Jiangyin Tianjiang Pharmaceutical Co Ltd
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Shandong Xuanzhu Pharma Co Ltd
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Abstract

The invention discloses a medical component with taurine and medicine to treat blood vessel of brain and heart disease, preparing method and usage in medical technical domain, which is characterized by the following: choosing the blood vessel of brain and heart disease medicine from one or several tanshinone IIA, medical salt, Notoginsen triterpenes, carthamus tinctorius yellow colour, haw leaf total flavone, puerarin and lamp-dish flower element; choosing tanshinone IIA or medical salt as tanshinone IIA mahogany. This invention can used to treat coronary disease, angina pectoris and so on.

Description

The compositions of the medicine of taurine and treatment cardiovascular and cerebrovascular disease
[technical field]
The present invention relates to a kind of pharmaceutical composition of mainly making and its production and use, belong to medical technical field by taurine and at least a medicine that is used for the treatment of cardiovascular and cerebrovascular disease.
[background technology]
In recent years along with living standard improves, rhythm of life is accelerated, and operating pressure increases, various cardiovascular and cerebrovascular diseases, sickness rate such as apoplexy, cerebrovascular blood supply insufficiency, hypertension, angina pectoris, myocardial infarction and sudden death rises day by day, and age of onset has trend in advance.Individuality over half is in sub-health state in the crowd who is engaged in mental work about 40 years old according to incompletely statistics, and 1/4th individual symptoms that occur cardiovascular and cerebrovascular disease are in one's early years arranged, and has 10% to suffer from comparatively serious coronary heart disease approximately.Cardiovascular and cerebrovascular disease is the high disease of a kind of disability rate, in case morbidity stays sequela easily, recovers difficulty.Therefore how effectively to treat cardiovascular and cerebrovascular disease and be still the problem that urgent clinical needs solve.
Taurine (taurine) is the abundantest free amino acid of content in the heart, accounts for 60% of total amount.Taurine and myocardium calcium and myocardial contraction have close ties.Taurine can increase the utilization of the calcium of myocardial contraction phase, the myocardial damage that the prevention calcium overload causes; and side effect such as increased heart rate and arrhythmia do not appear in treatment; when being used for the treatment of congestive heart failure; its clinical manifestation and cardiac status are clearly better, and also can significantly improve the myocardiac hemodynamics of valve ischemia.These functions all are very beneficial for the long-term treatment of chronic heart failure especially gerontal patient.In addition, the concentration of taurine is also very high in the platelet, is about 400～600 times of blood plasma, and the taurine in the platelet can suppress hematoblastic coagulation, has certain effect to preventing the thromboembolism that the incident collagen gathering of platelet causes.Taurine can reduce the level of cholesterol and low-density lipoprotein cholesterol in the blood, improves the HDL-C level simultaneously, and this is atherosis to prevention of arterial, coronary heart disease is useful.When body taurine shortage causes that taurine concentration reduces in the heart, will cause cardiac function to weaken, and then the cardiac trigger disease.Recently the content of taurine has the certain significance to diagnosis of heart disease in the report blood.Taurine raises to point out in the acute angina pectoris patient blood myocardial infarction.Taurine is included in " 2005 editions two ones 49 pages of Chinese pharmacopoeia as chemical drugs at present.Its structural formula is as follows:
Figure S06143898620060522D000011
Taurine
Tanshinone is one of effective ingredient of Treated with Radix Salviae Miltiorrhizae coronary heart disease, and the content in Radix Salviae Miltiorrhizae can reach more than 0.5%.Tanshinone is the effective ingredient of Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling.Tanshinone can increase coronary flow, improve the collateral circulation and the local blood supply of ischemic region cardiac muscle, improve the metabolism disorder of cardiac muscle, improve myocardial hypoxia tolerance, anticoagulant and antithrombotic form, dwindle laboratory animal ischemic myocardium infarct size, under doses, also can strengthen myocardial contraction.It is poor that tanshinone has intestinal absorption, the characteristics that clinical onset of action is slow, its sulfonation made sodium tanshinone IIA sulfate after, not only increased water solublity and helped preparation, and improved pharmacologically active.The standard of sodium tanshinone IIA sulfate has been indexed to the chemical drugs terrestrial reference and has risen the 10th 49 pages of GBs, and standard code contains C 19H 17NaO 6S calculates with dry product, must not be less than 96.0%.The sodium tanshinone IIA sulfate structural formula is as follows:
Figure S06143898620060522D000021
The sodium tanshinone IIA sulfate structural formula
Radix Notoginseng total arasaponins is the effective active composition that extracts from the Chinese medicine Radix Notoginseng, have the effect of invigorating blood circulation, can expand cardiovascular, increase coronary flow, suppress thrombosis, antiplatelet aggregation, and can dissolve established thrombosis, having additional nutrients property myocardial flow, can reduce the body oxygen consumption, improve body to anoxybiotic tolerance, expansion of cerebral vascular increases cerebral blood flow.Simultaneously, Radix Notoginseng also can reduce arterial pressure, slightly subtracts heart rate, and the heart working amount is lowered, thereby obviously reduces the oxygen consumption of cardiac muscle.In addition, experiment showed, that Radix Notoginseng total arasaponins all has to a certain degree antagonism to kinds of experiments arrhythmia model.Radix Notoginseng total arasaponins is used for the stasis of blood resistance of brain road, apoplectic hemiplegia, the resistance of the heart arteries and veins stasis of blood, obstruction of qi in the chest and cardialgia; Apoplexy sequela, angina pectoris belong to above-mentioned sign person.The standard of Radix Notoginseng total arasaponins has been recorded into the 19th 78 pages in the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation, and wherein regulation contains arasaponin R1 (C 47H 80O 18) should be not less than 2.0%; Ginsenoside Rg1 (C 42H 72O 14) should be not less than 28.0%; Ginsenoside Rb1 (C 54H 92O 23) should be not less than 25.0%; The total content that contains arasaponin R1, ginsenoside Rg1 and ginsenoside Rb1 should be not less than 55.0%.
Carthamus yellow is the water soluble mixt that contains multiple chalcone that extracts from Flos Carthami, and pharmacological evaluation proves that it is the main effectively active component of Flos Carthami.Carthamus yellow has coronary artery dilator, improves blood supply of cardiac muscle, brings high blood pressure down, and blood vessel dilating improves the organ blood supply, and anticoagulation suppresses multiple pharmacology's effects such as thrombosis.S-A Hydroxysafflor yellow A content is higher in the Carthamus yellow, has the pharmacodynamics effect representativeness.The Carthamus yellow raw material goes on the market, and has Zhejiang Yongning Pharmaceutical Factory and two families of Shanxi Huahui Kaide Pharmaceutical Co.,Ltd to produce.
Folium Crataegi total flavones is sundown or the pale brown toner end that extraction separation gets in the Folium Crataegi.Fructus Crataegi total flavones has pharmacological actions such as the coronary flow of increasing, blood pressure lowering, heart tonifying, arrhythmia, blood fat reducing and antiplatelet aggregation, has blood circulation promoting and blood stasis dispelling, the logical heart arteries and veins of a surname, the effect of the easypro network of regulating the flow of vital energy.The clinical chest distress that is used for, palpitation and amnesia, dizzy ear toot and angina pectoris, hyperlipidemia, diseases such as cerebral arterial insufficiency.One one 575～576 pages of Chinese Pharmacopoeia versions in 2005 under the Yixintong sheet item, have the standard of Folium Crataegi extract.Standard code, Folium Crataegi extract are pressed dry product and are calculated, and contain total flavones with anhydrous rutin (C 27H 30O 16) meter, must not be less than 80.0%; Contain hyperin (C 21H 20O 12), must not be less than 0.40%.
Puerarin be at first a kind of 8-β-D-glucopyanosyl-4 of obtaining by extraction separation in the Chinese medicine Radix Puerariae ', the 7-dihydroxy isoflavone at present can chemosynthesis.Puerarin has the increase myocardial flow, improves myocardial oxygen delivery, reduces platelet aggregation and blood viscosity, change the myocardial cell self-disciplining, prolong refractory stage, improve pharmacological actions such as arrhythmia, be widely used in the treatment of coronary heart disease, pulmonary heart disease, cerebral infarction etc. at present.Puerarin has recorded into second 688 pages of the 1st 77 pages of state-promulgated pharmacopoeia version in 2000 enlarged editions in 2002 two ones (increasing newly) and state-promulgated pharmacopoeia versions in 2005, and wherein regulation contains C 21H 20O 9Press dry product and calculate, must not be less than 97.0%.The puerarin structural formula is as follows:
Figure S06143898620060522D000031
The puerarin structural formula
Breviscapine is the effective ingredient that extracts from the Chinese medicine Herba Erigerontis.Breviscapine can improve brain blood circulation, cerebral blood flow increasing amount, reduces vascular resistance and anti-platelet aggregation, resists myocardial ischemia, strengthens myocardial contraction, improve energy metabolism of myocardial, coronary blood flow increasing, alleviate cardiac afterload, two-ways regulation blood pressure, be widely used in apoplexy sequela, coronary heart disease, angina pectoris.Breviscapine has recorded into the 20th 103 pages in the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation, and wherein content limit calculates for pressing dry product, contains lamp-dish flower acetic (C 12H 18O 12) should be 95.0%～105.0%.
Utilize one or more interactions in taurine and tanshinone or its pharmaceutically acceptable salt, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, the breviscapine at present; composition of prescription; be used to prepare the medicine of the medicine aspect for the treatment of cardiovascular and cerebrovascular disease, do not appear in the newspapers as yet.
[summary of the invention]
In order to meet clinical needs, treat cardiovascular and cerebrovascular disease better, the present invention uses the compatibility of some cardiovascular and cerebrovascular diseases medicaments commonly used and studies.Pleasantly surprised must the discovery; the pharmaceutical composition of making by the medicine of the taurine of effective dose and at least a treatment cardiovascular and cerebrovascular disease; have myocardial damage that very strong protection ischemia causes and brain injury, antithrombotic pharmacologically active, this has great significance to the treatment cardiovascular and cerebrovascular disease.The medicine of these treatment cardiovascular and cerebrovascular diseases is selected from: tanshinone or its pharmaceutically acceptable salt, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine.Taurine and these compatibility of drugss are used, and have significantly strengthened the curative effect of these medicines.
Pharmaceutical composition of the present invention, tanshinone pharmaceutically acceptable salt wherein is sulfonate, phosphate, maleate, fumarate, tartrate, mesylate, is preferably sodium tanshinone IIA sulfate.
Pharmaceutical composition of the present invention; the crude drug that comprises following parts by weight: 500～15000 parts of taurines; the medicine of treatment cardiovascular and cerebrovascular disease is different and different according to medicine; for sodium tanshinone IIA sulfate is 2～50 parts; for Radix Notoginseng total arasaponins is 20～500 parts, is 10～250 parts for Carthamus yellow, is 10～250 parts for Folium Crataegi total flavones; for puerarin is 20～1000 parts, is 1～50 part for breviscapine.
Pharmaceutical composition of the present invention; the weight portion of crude drug is preferably: 1500～6000 parts of taurines; the medicine of treatment cardiovascular and cerebrovascular disease is different and different according to medicine; for sodium tanshinone IIA sulfate is 5～20 parts; for Radix Notoginseng total arasaponins is 50～200 parts, is 25～100 parts for Carthamus yellow, is 25～100 parts for Folium Crataegi total flavones; for puerarin is 100～400 parts, is 2～10 parts for breviscapine.
Pharmaceutical composition of the present invention; the weight portion optimum of crude drug is: 3000 parts of taurines; the medicine of treatment cardiovascular and cerebrovascular disease is different and different according to medicine; for sodium tanshinone IIA sulfate is 10 parts; for Radix Notoginseng total arasaponins is 100 parts, is 50 parts for Carthamus yellow, is 50 parts for Folium Crataegi total flavones; for puerarin is 200 parts, is 5 parts for breviscapine.
More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight portion between each composition.
The ratio of above weight portion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The consumption of drug component of the present invention is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.
Pharmaceutical composition of the present invention is mainly used in the treatment of diseases such as coronary heart disease, angina pectoris, cerebral arterial insufficiency, apoplexy sequela.
Pharmaceutical composition of the present invention can add one or more pharmaceutically acceptable carriers, is applied to the patient of this treatment of needs in the mode of oral or parenteral.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred dosage form of this compositions is oral formulations or injection, as sheet, capsule, granule, powder pin, liquid drugs injection, transfusion etc.
Pharmaceutical composition of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
Pharmaceutical composition of the present invention in order to increase its dissolubility, can add solubilizing agents such as polyoxyethylene sorbitan monoleate, polyethylene glycols, propylene glycol, glycerol when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
Pharmaceutical composition of the present invention is when making oral formulations, and selectable filler has: starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.; Selectable binding agent has: sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methylcellulose, ethyl cellulose, hypromellose, gelling starch etc.; Selectable disintegrating agent has: dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Selectable lubricant has: magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.
The present composition has the following advantages:
(1) provides the compatibility of drugs of a kind of taurine and at least a treatment cardiovascular and cerebrovascular disease to be used for pharmaceutical composition of treatment of diseases such as coronary heart disease, angina pectoris, cerebral arterial insufficiency, apoplexy sequela and its production and use first, satisfied urgent clinical needs.
(2) we have carried out pharmacological research to the interaction and the composition of prescription of various pharmaceutical compositions of the present invention; find pleasantly surprisedly; one or more combination drugs in taurine and sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, the breviscapine can significantly strengthen the pharmacologically active of these medicines.Pharmacological experiment study shows, each pharmaceutical composition of the present invention, and significantly Chinese People's Anti-Japanese Military and Political College Mus expeirmental myocardial ischemia dwindles the area (p＜0.01, p＜0.001) of ischemic myocardium infarction; The inductive platelet aggregation of remarkable anti-ADP (p＜0.01, p＜0.001); But significant prolongation rat carotid artery thrombus formation time (p＜0.01, p＜0.001) has anti-thrombosis function; Can significantly reduce PLA 2Active (p＜0.01, p＜0.001) improves cerebral circulation, alleviates cerebral ischemia reperfusion injury, thus the performance cerebral protection.And its taurine, sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, individually dosed effect (p＜0.05, p＜0.01) of breviscapine of being better than evident in efficacy.Compatibility is used, and has produced beyond thought effect.
(3) each preparation of pharmaceutical composition of the present invention, preparation technology is simple, and mass discrepancy is little between the different batches medicine, and drug quality is uniform and stable.
(4) acute toxicity test shows that pharmaceutical composition toxicity of the present invention is little, and safety range is big.
(5) the stability test result shows that every index of drug combination preparation of the present invention is all more stable, has guaranteed safety of clinical administration.
(6) pharmaceutical composition drug combination determined curative effect of the present invention, and reduced relative dosage, be with a wide range of applications.
Below further set forth the beneficial effect of medicine of the present invention by testing example.In the following test example: the compositions of taurine, sodium tanshinone IIA sulfate is called for short The NIUDAN compositionsThe compositions of taurine, Radix Notoginseng total arasaponins is called for short Cattle three compositionssThe compositions of taurine, Carthamus yellow is called for short The red compositions of cattleThe compositions of taurine, Folium Crataegi total flavones is called for short The Ox Mountain compositionsThe compositions of taurine, puerarin is called for short Cattle Pueraria lobota compositionsThe compositions of taurine, breviscapine is called for short Cattle lamp compositions
Test example 1 pharmaceutical composition of the present invention is to the influence of rat experiment myocardial inyaretion scope
Animal subject: Wistar rat, male and female half and half, body weight 203～228g.
The test sample taurine injection, self-control, 5ml: 300mg;
The sodium tanshinone IIA sulfate injection, Shanghai No.1 Bio-Chemical Pharmacetical Industry Co., Ltd, 2ml: 10mg;
XUESAITONG (Radix Notoginseng total arasaponins) injection, Kunming Medicine Group Stock Co., Ltd, 2ml: 0.1g;
The injection Carthamus yellow, Zhejiang Yongning Pharmaceutical Factory, every bottled 50mg;
The Folium Crataegi total flavones injection, self-control, 2ml: 50mg;
Puerarin injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml: 100mg;
Breviscapini injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml: 5mg;
The NIUDAN injection, self-control is with reference to 1 preparation of embodiment 1 prescription;
Cattle three injection, self-control is with reference to 2 preparations of embodiment 1 prescription;
The red injection of cattle, self-control is with reference to 3 preparations of embodiment 1 prescription;
The Ox Mountain injection, self-control is with reference to 4 preparations of embodiment 1 prescription;
Cattle Pueraria lobota injection, self-control is with reference to 5 preparations of embodiment 1 prescription;
Cattle lamp injection, self-control is with reference to 6 preparations of embodiment 1 prescription.
Test method: get 260 of rats; be divided into 26 groups at random; every group 10, be respectively: normal saline group, taurine group, sodium tanshinone IIA sulfate group, Radix Notoginseng total arasaponins group, Carthamus yellow group, Folium Crataegi total flavones group, puerarin group, breviscapine group, the basic, normal, high dosage group of NIUDAN compositions, the basic, normal, high dosage group of cattle three compositionss, the basic, normal, high dosage group of the red compositions of cattle, the basic, normal, high dosage group of Ox Mountain compositions, the basic, normal, high dosage group of cattle Pueraria lobota compositions, the basic, normal, high dosage group of cattle lamp compositions.
The rat experiment myocardial infarction model: it is fixing that animal pentobarbital intraperitoneal injection of anesthesia (45mg/kg) is faced upward the position.Tracheal intubation is made the longitudinal incision of 2cm in breastbone left side, nearly breastbone side is cut off the 3rd, the 4th costicartilage, open the thoracic cavity after, connect artificial respirator (ventilation 2ml/100g, 50 times/min).Cut off pericardium, expose heart, left anterior descending coronary artery root threading is in order to ligation, and record standard II lead electrocardiogram was stablized 10 minutes, and the ligation left anterior descending coronary artery is closed the thoracic cavity.With syringe sucking-off animal throat secretions, make animal recover autonomous respiration.Behind the ligation coronary artery 15min, intravenous administration, dosage such as following table.Behind the ligation coronary artery 4 hours, win heart, 5 of the following crosscuts of ligature, carry out chlorination nitro blue tetrazolium (N-BT) dyeing, calculating myocardium infarcted region area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).The results are shown in Table 1a
Table 1 pharmaceutical composition of the present invention is to the influence of rat experiment myocardial inyaretion scope
Figure S06143898620060522D000061
Annotate: compare with the normal saline matched group, *P＜0.05, *P＜0.01, * *P＜0.001; Compare with the taurine group, aP＜0.01, bP＜0.001; Compare with the sodium tanshinone IIA sulfate group, cP＜0.05, dP＜0.01; Compare with the Radix Notoginseng total arasaponins group, eP＜0.05, fP＜0.01; Compare with the Carthamus yellow group, gP＜0.05, hP＜0.01; Compare with the Folium Crataegi total flavones group, iP＜0.05, jP＜0.01; Compare with the sodium tanshinone IIA sulfate group, kP＜0.05, lP＜0.01; Compare with the sodium tanshinone IIA sulfate group, mP＜0.05, nP＜0.01.
Result of the test and conclusion result of the test see Table 1.
(1) compares with the normal saline matched group, the sodium tanshinone IIA sulfate group, the Radix Notoginseng total arasaponins group, the Carthamus yellow group, the Folium Crataegi total flavones group, the puerarin group, the breviscapine group, the NIUDAN compositions is low, in, high dose group, cattle three compositionss are low, in, high dose group, the red compositions of cattle is low, in, high dose group, the Ox Mountain compositions is low, in, high dose group, cattle Pueraria lobota compositions is low, in, high dose group, cattle lamp compositions is low, in, high dose group all has significant function of resisting myocardial ischemia, can dwindle area (p＜0.05 of experimental rat ischemic myocardial infarction, p＜0.01, p＜0.001).
(2) compare with the taurine group, NIUDAN compositions low dose group, cattle three compositions low dose group, the red compositions low dose group of cattle, Ox Mountain compositions low dose group, cattle Pueraria lobota compositions low dose group, cattle lamp compositions low dose group all have significant function of resisting myocardial ischemia (p＜0.01); The middle and high dosage group of NIUDAN compositions, the middle and high dosage group of cattle three compositionss, the middle and high dosage group of the red compositions of cattle, the middle and high dosage group of Ox Mountain compositions, the middle and high dosage group of cattle Pueraria lobota compositions, the middle and high dosage group of cattle lamp compositions all have extremely significant function of resisting myocardial ischemia (p＜0.001).
(3) compare NIUDAN compositions low dose group can resist myocardial ischemia significantly (p＜0.05) with the sodium tanshinone IIA sulfate group; But the middle and high dosage group of the NIUDAN compositions utmost point resists myocardial ischemia significantly (p＜0.01).
(4) compare cattle three compositions low dose group can resist myocardial ischemia significantly (p＜0.05) with the Radix Notoginseng total arasaponins group; But the middle and high dosage group of the cattle three compositionss utmost point resists myocardial ischemia significantly (p＜0.01).
(5) compare the red compositions low dose group of cattle can resist myocardial ischemia significantly (p＜0.05) with the Carthamus yellow group; But the middle and high dosage group of the red compositions of the cattle utmost point resists myocardial ischemia significantly (p＜0.01).
(6) compare Ox Mountain compositions low dose group can resist myocardial ischemia significantly (p＜0.05) with the Folium Crataegi total flavones group; But the middle and high dosage group of the Ox Mountain compositions utmost point resists myocardial ischemia significantly (p＜0.01).
(7) compare cattle Pueraria lobota compositions low dose group can resist myocardial ischemia significantly (p＜0.05) with the puerarin group; But the middle and high dosage group of the cattle Pueraria lobota compositions utmost point resists myocardial ischemia significantly (p＜0.01).
(8) compare cattle lamp compositions low dose group can resist myocardial ischemia significantly (p＜0.05) with breviscapine; But the middle and high dosage group of the cattle lamp compositions utmost point resists myocardial ischemia significantly (p＜0.01).
Result of the test shows; each pharmaceutical composition of the present invention is Chinese People's Anti-Japanese Military and Political College Mus expeirmental myocardial ischemia significantly; dwindle the area of ischemic myocardium infarction; and its taurine, sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, individually dosed effect of breviscapine of being better than evident in efficacy; prompting taurine and sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine combination drug; effect with Synergistic can significantly strengthen the curative effect of these medicines aspect resisting myocardial ischemia.
Test example 2 pharmaceutical composition antiplatelet aggregative activities of the present invention
Experimental animal: Wistar rat, male and female half and half, body weight 206～225g.
The test sample taurine injection, self-control, 5ml: 300mg;
The sodium tanshinone IIA sulfate injection, Shanghai No.1 Bio-Chemical Pharmacetical Industry Co., Ltd, 2ml:10mg;
XUESAITONG (Radix Notoginseng total arasaponins) injection, Kunming Medicine Group Stock Co., Ltd, 2ml:0.1g;
The injection Carthamus yellow, Zhejiang Yongning Pharmaceutical Factory, every bottled 50mg;
The Folium Crataegi total flavones injection, self-control, 2ml:50mg;
Puerarin injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml:100mg;
Breviscapini injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml:5mg;
The NIUDAN injection, self-control is with reference to 1 preparation of embodiment 1 prescription;
Cattle three injection, self-control is with reference to 2 preparations of embodiment 1 prescription;
The red injection of cattle, self-control is with reference to 3 preparations of embodiment 1 prescription;
The Ox Mountain injection, self-control is with reference to 4 preparations of embodiment 1 prescription;
Cattle Pueraria lobota injection, self-control is with reference to 5 preparations of embodiment 1 prescription;
Cattle lamp injection, self-control is with reference to 6 preparations of embodiment 1 prescription.
Test method: get 260 of rats; be divided into 26 groups at random; every group 10, be respectively: normal saline group, taurine group, sodium tanshinone IIA sulfate group, Radix Notoginseng total arasaponins group, Carthamus yellow group, Folium Crataegi total flavones group, puerarin group, breviscapine group, the basic, normal, high dosage group of NIUDAN compositions, the basic, normal, high dosage group of cattle three compositionss, the basic, normal, high dosage group of the red compositions of cattle, the basic, normal, high dosage group of Ox Mountain compositions, the basic, normal, high dosage group of cattle Pueraria lobota compositions, the basic, normal, high dosage group of cattle lamp compositions.Each treated animal intraperitoneal injection, once a day, successive administration 7 days, after the last administration 1 hour, from abdominal aortic blood, anticoagulant adopted 3.28% sodium citrate after the Animal Anesthesia, with blood with 1: 9 mixed.With anticoagulated whole blood 1500r.min under 20 ℃ of conditions -1Centrifugal 5min obtains platelet rich plasma (PRP).After leaving and taking quantitative PRP, will remain PRP once more with 3000r.min -1Centrifugal 10min obtains own control platelet rich plasma (PPP).Regulate PRP concentration with PPP, make each PRP concentration identical.In 37 ℃ constant temperature hole after the preheating, (final concentration is 3 μ mol.L to add ADP with PRP -1) cause and write down maximum agglutination rate by platelet aggregation.The results are shown in Table 2.
The antiplatelet aggregative activity of table 2 pharmaceutical composition of the present invention
Figure DEST_PATH_G06143898620080115D000011
Annotate: compare with the normal saline matched group, *P＜0.05, *P (0.01, * *P＜0.001; Compare with the taurine group, aP＜0.01, bP＜0.001; Compare with the sodium tanshinone IIA sulfate group, cP＜0.05, dP＜0.01; Compare with the Radix Notoginseng total arasaponins group, eP＜0.05, fP＜0.01; Compare with the Carthamus yellow group, gP＜0.05, hP＜0.01; Compare with the Folium Crataegi total flavones group, iP＜0.05, iP＜0.01; Compare with the sodium tanshinone IIA sulfate group, kP＜0.05, lP＜0.01; Compare with the sodium tanshinone IIA sulfate group, mP＜0.05, nP＜0.01.
Result of the test and conclusion result of the test see Table 2.
(1) compares with the normal saline matched group, sodium tanshinone IIA sulfate group, Radix Notoginseng total arasaponins group, Carthamus yellow group, Folium Crataegi total flavones group, puerarin group, breviscapine group, the basic, normal, high dosage group of NIUDAN compositions, the basic, normal, high dosage group of cattle three compositionss, the basic, normal, high dosage group of the red compositions of cattle, the basic, normal, high dosage group of Ox Mountain compositions, the basic, normal, high dosage group of cattle Pueraria lobota compositions, the basic, normal, high dosage group of cattle lamp compositions all have significant antiplatelet aggregative activity (p＜0.05, p＜0.01, p＜0.001).
(2) compare with the taurine group, NIUDAN compositions low dose group, cattle three compositions low dose group, the red compositions low dose group of cattle, Ox Mountain compositions low dose group, cattle Pueraria lobota compositions low dose group, cattle lamp compositions low dose group all have significant antiplatelet aggregative activity (p＜0.01); The middle and high dosage group of NIUDAN compositions, the middle and high dosage group of cattle three compositionss, the middle and high dosage group of the red compositions of cattle, the middle and high dosage group of Ox Mountain compositions, the middle and high dosage group of cattle Pueraria lobota compositions, the middle and high dosage group of cattle lamp compositions all have extremely significant antiplatelet aggregative activity (p＜0.001).
(3) compare with the sodium tanshinone IIA sulfate group, NIUDAN compositions low dose group is antiplatelet aggregation (p＜0.05) significantly; But the middle and high dosage group of the NIUDAN compositions utmost point is antiplatelet aggregation (p＜0.01) significantly.
(4) compare with the Radix Notoginseng total arasaponins group, cattle three compositions low dose group are antiplatelet aggregation (p＜0.05) significantly; But the middle and high dosage group of the cattle three compositionss utmost point is antiplatelet aggregation (p＜0.01) significantly.
(5) compare with the Carthamus yellow group, the red compositions low dose group of cattle is antiplatelet aggregation (p＜0.05) significantly; But the middle and high dosage group of the red compositions of the cattle utmost point is antiplatelet aggregation (p＜0.01) significantly.
(6) compare with the Folium Crataegi total flavones group, Ox Mountain compositions low dose group is antiplatelet aggregation (p＜0.05) significantly; But the middle and high dosage group of the Ox Mountain compositions utmost point is antiplatelet aggregation (p＜0.01) significantly.
(7) compare with the puerarin group, cattle Pueraria lobota compositions low dose group is antiplatelet aggregation (p＜0.05) significantly; But the middle and high dosage group of the cattle Pueraria lobota compositions utmost point is antiplatelet aggregation (p＜0.01) significantly.
(8) compare with breviscapine, cattle lamp compositions low dose group is antiplatelet aggregation (p＜0.05) significantly; But the middle and high dosage group of the cattle lamp compositions utmost point is antiplatelet aggregation (p＜0.01) significantly.
Result of the test shows; each pharmaceutical composition of the present invention can the inductive platelet aggregation of remarkable anti-ADP; has anti thrombotic action; and its taurine, sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, individually dosed effect of breviscapine of being better than evident in efficacy; combination drug in prompting taurine and sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, the breviscapine; effect with Synergistic can significantly strengthen the curative effect of these medicines aspect antiplatelet aggregation.
Test example 3 pharmaceutical compositions of the present invention are to thrombotic influence in the rat carotid artery
Experimental animal: Wistar rat, male and female half and half, body weight 210～230g.
The test sample taurine injection, self-control, 5ml: 300mg;
The sodium tanshinone IIA sulfate injection, Shanghai No.1 Bio-Chemical Pharmacetical Industry Co., Ltd, 2ml: 10mg;
XUESAITONG (Radix Notoginseng total arasaponins) injection, Kunming Medicine Group Stock Co., Ltd, 2ml: 0.1g;
The injection Carthamus yellow, Zhejiang Yongning Pharmaceutical Factory, every bottled 50mg;
The Folium Crataegi total flavones injection, self-control, 2ml: 50mg;
Puerarin injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml: 100mg;
Breviscapini injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml: 5mg;
The NIUDAN injection, self-control is with reference to 1 preparation of embodiment 1 prescription;
Cattle three injection, self-control is with reference to 2 preparations of embodiment 1 prescription;
The red injection of cattle, self-control is with reference to 3 preparations of embodiment 1 prescription;
The Ox Mountain injection, self-control is with reference to 4 preparations of embodiment 1 prescription;
Cattle Pueraria lobota injection, self-control is with reference to 5 preparations of embodiment 1 prescription;
Cattle lamp injection, self-control is with reference to 6 preparations of embodiment 1 prescription.
Test method: get 260 of rats; be divided into 26 groups at random; every group 10, be respectively: normal saline group, taurine group, sodium tanshinone IIA sulfate group, Radix Notoginseng total arasaponins group, Carthamus yellow group, Folium Crataegi total flavones group, puerarin group, breviscapine group, the basic, normal, high dosage group of NIUDAN compositions, the basic, normal, high dosage group of cattle three compositionss, the basic, normal, high dosage group of the red compositions of cattle, the basic, normal, high dosage group of Ox Mountain compositions, the basic, normal, high dosage group of cattle Pueraria lobota compositions, the basic, normal, high dosage group of cattle lamp compositions.Each organizes intraperitoneal injection.Model group gives the isometric(al) normal saline, and administration begins test after 20 minutes.Animal is with 2.5% pentobarbital sodium (25mg/kg) intraperitoneal injection of anesthesia, the rat dorsal position is fixed, separate right carotid, adopt electrical injuries carotid artery intima method, form instrument with the experimental thrombus in vivo of BT87-3 and measure different group animal carotid artery thrombus formation time.Electrode is seated on the carotid artery it carried out electricity irritation (2mA 7min), with induction electrode continuous measurement arterial distal surface temperature, observes the tremulous pulse temperature bust time.The record electricity irritation began to the time of aorta temperature bust, and this time is decided to be carotid artery thrombus formation time (surpassing 3000 seconds persons in 3000 seconds).Experimental result sees Table 3.
Table 3 pharmaceutical composition of the present invention is to thrombotic influence in the rat carotid artery
Annotate: compare with the normal saline matched group, *P＜0.01, * *P＜0.001; Compare with the taurine group, aP＜0.01, bP＜0.001; Compare with the sodium tanshinone IIA sulfate group, cP＜0.05, dP＜0.01; Compare with the Radix Notoginseng total arasaponins group, eP＜0.05, fP＜0.01; Compare with the Carthamus yellow group, gP＜0.05, hP＜0.01; Compare with the Folium Crataegi total flavones group, iP＜0.05, jP＜0.01; Compare with the sodium tanshinone IIA sulfate group, kP＜0.05, lP＜0.01; Compare with the sodium tanshinone IIA sulfate group, mP＜0.05, nP＜0.01.
Result of the test and conclusion result of the test see Table 3.
(1) compares with the normal saline matched group; the taurine group; the sodium tanshinone IIA sulfate group; the Radix Notoginseng total arasaponins group; the Carthamus yellow group; the Folium Crataegi total flavones group; the puerarin group; the breviscapine group; the NIUDAN compositions is low; in; high dose group; cattle three compositionss are low; in; high dose group; the red compositions of cattle is low; in; high dose group; the Ox Mountain compositions is low; in; high dose group; cattle Pueraria lobota compositions is low; in; high dose group; cattle lamp compositions is low; in; but high dose group is significant prolongation rat carotid artery thrombus formation time all; has antithrombotic effect (p＜0.01, p＜0.001).
(2) compare with the taurine group, but the equal significant prolongation rat carotid artery thrombus formation time of NIUDAN compositions low dose group, cattle three compositions low dose group, the red compositions low dose group of cattle, Ox Mountain compositions low dose group, cattle Pueraria lobota compositions low dose group, cattle lamp compositions low dose group
(p＜0.01); But the middle and high dosage group of NIUDAN compositions, the middle and high dosage group of cattle three compositionss, the middle and high dosage group of the red compositions of cattle, the middle and high dosage group of Ox Mountain compositions, the middle and high dosage group of cattle Pueraria lobota compositions, the middle and high dosage group of cattle lamp compositions be utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.001) all.
(3) compare with the sodium tanshinone IIA sulfate group, but NIUDAN compositions low dose group significant prolongation rat carotid artery thrombus formation time (p＜0.05); But the middle and high dosage group of NIUDAN compositions utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.01).
(4) compare with the Radix Notoginseng total arasaponins group, but cattle three compositions low dose group significant prolongation rat carotid artery thrombus formation time (p＜0.05); But the middle and high dosage group of cattle three compositionss utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.01).
(5) compare with the Carthamus yellow group, but the red compositions low dose group of cattle significant prolongation rat carotid artery thrombus formation time (p＜0.05); But the middle and high dosage group of the red compositions of cattle utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.01).
(6) compare with the Folium Crataegi total flavones group, but Ox Mountain compositions low dose group significant prolongation rat carotid artery thrombus formation time (p＜0.05); But the middle and high dosage group of Ox Mountain compositions utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.01).
(7) compare with the puerarin group, but cattle Pueraria lobota compositions low dose group significant prolongation rat carotid artery thrombus formation time (p＜0.05); But the middle and high dosage group of cattle Pueraria lobota compositions utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.01).
(8) compare with breviscapine, but cattle lamp compositions low dose group significant prolongation rat carotid artery thrombus formation time (p＜0.05); But the middle and high dosage group of cattle lamp compositions utmost point significant prolongation rat carotid artery thrombus formation time (p＜0.01).
Result of the test shows; but each pharmaceutical composition significant prolongation rat carotid artery thrombus formation time of the present invention; has anti-thrombosis function; and its taurine that is better than evident in efficacy; sodium tanshinone IIA sulfate; Radix Notoginseng total arasaponins; Carthamus yellow; Folium Crataegi total flavones; puerarin; the effect that breviscapine is individually dosed; prompting taurine and sodium tanshinone IIA sulfate; Radix Notoginseng total arasaponins; Carthamus yellow; Folium Crataegi total flavones; puerarin; the breviscapine combination drug; effect with Synergistic is in prolong rats carotid artery thrombus formation time; antithrombotic formation aspect can significantly strengthen the curative effect of these medicines.
Test example 4 pharmaceutical compositions of the present invention are to the protective effect of Medulla Leporis seu Oryctolagi ischemical reperfusion injury
Experimental animal: rabbit, body weight 2.2～2.6kg, male and female half and half.
The test sample taurine injection, self-control, 5ml: 300mg;
The sodium tanshinone IIA sulfate injection, Shanghai No.1 Bio-Chemical Pharmacetical Industry Co., Ltd, 2ml: 10mg;
XUESAITONG (Radix Notoginseng total arasaponins) injection, Kunming Medicine Group Stock Co., Ltd, 2ml: 0.1g;
The injection Carthamus yellow, Zhejiang Yongning Pharmaceutical Factory, every bottled 50mg;
The Folium Crataegi total flavones injection, self-control, 2ml: 50mg;
Puerarin injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml: 100mg;
Breviscapini injection, Sida Pharmaceutical Co Ltd, Hainan, 2ml: 5mg;
The NIUDAN injection, self-control is with reference to 1 preparation of embodiment 1 prescription;
Cattle three injection, self-control is with reference to 2 preparations of embodiment 1 prescription;
The red injection of cattle, self-control is with reference to 3 preparations of embodiment 1 prescription;
The Ox Mountain injection, self-control is with reference to 4 preparations of embodiment 1 prescription;
Cattle Pueraria lobota injection, self-control is with reference to 5 preparations of embodiment 1 prescription;
Cattle lamp injection, self-control is with reference to 6 preparations of embodiment 1 prescription.
Test method: get 240 of rabbit, be divided at random: ischemia-reperfusion group (I/R group), NIUDAN combination treatment group, cattle three combination treatment groups, the red combination treatment group of cattle, Ox Mountain combination treatment group, cattle Pueraria lobota combination treatment group, cattle lamp combination treatment group, sodium tanshinone IIA sulfate treatment group, Radix Notoginseng total arasaponins treatment group, Carthamus yellow treatment group, Folium Crataegi total flavones treatment group, puerarin treatment group, breviscapine treatment group and Sham-operated control group (SOC group).
(1) ischemia-reperfusion group (I/R group): 18, urethane ester solution 1g/kg body weight auricular vein anesthesia with 25%, the cervical region median incision separates trachea and inserts tracheal casing pipe, expose bilateral carotid, close 20min with bulldog clamp both sides folder, cause cerebral ischemia, pine folder pours into 1h, 6h and 12h respectively again, each 6 of three time points.Behind pine folder 10min, auricular vein is injected normal saline 5ml/kg body weight respectively.
(2) NIUDAN combination treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected NIUDAN composite injection 903mg/kg respectively.
(3) cattle three combination treatment groups: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected cattle three composite injection 930mg/kg respectively.
(4) the red combination treatment group of cattle: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected the red composite injection 915mg/kg of cattle respectively.
(5) Ox Mountain combination treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected Ox Mountain composite injection 915mg/kg respectively.
(6) cattle Pueraria lobota combination treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected cattle Pueraria lobota composite injection 960mg/kg respectively.
(7) cattle lamp combination treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected cattle lamp composite injection 901.5mg/kg respectively.
(8) sodium tanshinone IIA sulfate treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected sodium tanshinone IIA sulfate injection 6mg/kg respectively.
(9) Radix Notoginseng total arasaponins group treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected XUESAITONG (Radix Notoginseng total arasaponins group) injection 30mg/kg respectively.
(10) Carthamus yellow group treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein pushes away Carthamus yellow group injection 15mg/kg respectively.
(11) Folium Crataegi total flavones treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected Folium Crataegi total flavones injection 15mg/kg respectively.
(12) puerarin treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected puerarin injection 60mg/kg respectively.
(13) breviscapine treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected Breviscapini injection 6mg/kg respectively.
(14) Sham-operated control group (SOC group): 6, animal only row anesthesia and tremulous pulse exclusion and not pressing from both sides closes, and puts to death behind the 1h.Above-mentioned each group promptly breaks end after testing and finishing, and strips out brain in ice bath, separates on the ice pan and cuts bilateral hippocampus tissue, is placed in 4 ℃ of refrigerators with the tinfoil parcel to store, and is standby.Use the pH acidometer and detect hippocampal tissue PLA 2Activity; Adopt the weight in wet base method of doing, TTC staining mensuration cortex brain water content, infarct size; Light microscopic is observed the cerebral tissue pathological change down.
Result of the test: (1) is to hippocampal tissue PLA 2After active influence: I/R group is poured into 1h, 6h and 12h again, hippocampal tissue PLA 2Activity obviously increases (p＜0.01) than SOC, and prolongs PLA with infusion time 2The activity trend that tapers off, but comparing difference not significantly (p＞0.05) between each time point; NIUDAN combination treatment group, cattle three combination treatment groups, the red combination treatment group of cattle, Ox Mountain combination treatment group, cattle Pueraria lobota combination treatment group, cattle lamp combination treatment group (1h, 6h, 12h) PLA 2Active obviously reduction relatively has significant difference (p＜0.01, p＜0.001) with SOC group and each corresponding time point of I/R, and with infusion time prolongation again, PLA 2Activity is recovered to normal level gradually; Sodium tanshinone IIA sulfate treatment group, Radix Notoginseng total arasaponins treatment group, Carthamus yellow treatment group, Folium Crataegi total flavones treatment group, puerarin treatment group and breviscapine treatment group (1h, 6h, 12h) PLA 2The active reduction relatively has notable difference (p＜0.05, p＜0.01) with SOC group and each corresponding time point of I/R.
(2) to the influence of cortical tissue's water content (%) and infarct size (%): I/R organizes each time point brain water content and all increases; NIUDAN combination treatment group, cattle three combination treatment groups, the red combination treatment group of cattle, Ox Mountain combination treatment group, cattle Pueraria lobota combination treatment group, each time point brain water content of cattle lamp combination treatment group are compared obviously with the I/R group and are alleviated (p＜0.001), and brain infarction area is compared obviously with the I/R group and dwindled (p＜0.01); Sodium tanshinone IIA sulfate treatment group, Radix Notoginseng total arasaponins treatment group, Carthamus yellow treatment group, Folium Crataegi total flavones treatment group, puerarin treatment group with breviscapine treatment organize each time point brain water content and I/R group and compare all and alleviate (p＜0.01), brain infarction area is compared all with the I/R group and is dwindled (p＜0.05, p＜0.01).
(3) brain tissue pathology change: SOC organizes no infarction kitchen range, and the neuronal structure form is normal, continuously the matter edema; The I/R group has the infarction kitchen range, the neuron swelling of infarction kitchen range week, and cell outline is unclear, and interstitial edema is obvious; NIUDAN combination treatment group, cattle three combination treatment groups, the red combination treatment group of cattle, Ox Mountain combination treatment group, cattle Pueraria lobota combination treatment group, cattle lamp combination treatment group, sodium tanshinone IIA sulfate treatment group, Radix Notoginseng total arasaponins treatment group, Carthamus yellow treatment group, Folium Crataegi total flavones treatment group, puerarin treatment group and breviscapine treatment group infarction kitchen range area all dwindle, the neuron swelling of infarction kitchen range week is not obvious, and interstitial edema obviously alleviates; Each medicine composite for curing group effect of the present invention is more obvious.
Conclusion: above-mentioned result of the test shows that each pharmaceutical composition of the present invention, sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin and breviscapine all can be by reducing PLA 2Activity is improved cerebral circulation, alleviates cerebral ischemia reperfusion injury, thus the performance cerebral protection.And the every index of each medicine composite for curing group of the present invention all is better than taurine, sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, the individually dosed effect of breviscapine; prompting taurine and sodium tanshinone IIA sulfate, Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine combination drug; effect with Synergistic; aspect the treatment cerebral ischemia reperfusion injury, can significantly strengthen the curative effect of these medicines.
Test example 5 medicine composition injection acute toxicity testings of the present invention
(1) test method
Test sample:
The NIUDAN injection, self-control, specification: 10ml derives from embodiment 1 prescription 1;
Cattle three injection, self-control, specification: 10ml derives from embodiment 1 prescription 2;
The red injection of cattle, self-control, specification: 10ml derives from embodiment 1 prescription 3;
The Ox Mountain injection, self-control, specification: 10ml derives from embodiment 1 prescription 4;
Cattle Pueraria lobota injection, self-control, specification: 10ml derives from embodiment 1 prescription 5;
Cattle lamp injection, self-control, specification: 10ml derives from embodiment 1 prescription 6.
Animal subject: mice, each 5 of every group of male and female, male body weight 25～28g, female body weight 21～24g.
Route of administration: intravenous injection, lumbar injection.
Observe special project: death toll, general state, body weight, cut open inspection, half lethal dose.
(2) result of the test
Require to carry out prerun according to acute toxicity test, lumbar injection and intravenous injection two route of administration all can't be measured the median lethal dose(LD 50) of medicine, also do not see tangible toxic reaction, so carry out a day maximum dosage-feeding test.Dosage: tail vein injection 0.2ml/10g, lumbar injection 0.2ml/10g, 2 times on the one.
Death toll: do not occur dead.
General state: no abnormality seen changes.
Body weight: in administration preceding 1 day, administration day, measured in 2,4,6,8,10,12,14 days after the administration; No abnormality seen changes.
Cut open inspection: the heart, liver, lung, kidney etc. organize no abnormality seen to change.
(3) conclusion
Occur death in this experiment, KLH composite injection I, KLH composite injection II are 0.4ml/10g to the maximum tolerated dose of male and female mouse vein and intraperitoneal injection, are equivalent to 120 times of maximum consumption 20ml of the 60kg body weight day for human beings.Show this product low toxicity, safe.
Test example 6 medicine composition injection stability experiments of the present invention
Test sample:
The NIUDAN injection, self-control, specification: 10ml derives from embodiment 1 prescription 1;
Cattle three injection, self-control, specification: 10ml derives from embodiment 1 prescription 2;
The red injection of cattle, self-control, specification: 10ml derives from embodiment 1 prescription 3;
The Ox Mountain injection, self-control, specification: 10ml derives from embodiment 1 prescription 4;
Cattle Pueraria lobota injection, self-control, specification: 10ml derives from embodiment 1 prescription 5;
Cattle lamp injection, self-control, specification: 10ml derives from embodiment 1 prescription 6.
Investigation project: character, content, related substance.
Result: long-time stability experimental technique and result: each compositions of this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, and experimental result shows that the long-term placement of each medicine composition injection of the present invention is basicly stable.
[specific embodiment]
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.
The preparation of embodiment 1 pharmaceutical composition aqueous injection of the present invention
Prescription:
Prescription 1: NIUDAN injection
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 2: cattle three injection
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 3: the red injection of cattle
Taurine 3kg
Carthamus yellow 50g
Polyoxyethylene sorbitan monoleate 40g
PEG400 200ml
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 4: Ox Mountain injection
Taurine 3kg
Folium Crataegi total flavones 50g
Polyoxyethylene sorbitan monoleate 50g
PEG400 300ml
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 5: cattle Pueraria lobota injection
Taurine 3kg
Puerarin 200g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 6: cattle lamp injection
Taurine 3kg
Breviscapine 5g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Water for injection adds to 10000ml
Prepare 1000 altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) polyoxyethylene sorbitan monoleate is made 40% aqueous solution, the heated and stirred dissolving fully to add the sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) of recipe quantity; PEG400 adds the water for injection mixing of dosing amount 50%, adds the taurine of recipe quantity again, and the heated and stirred dissolving fully.
3) merge above-mentioned two kinds of solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.05%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) with the solution sealing by fusing in glass ampule.
9) 100 ℃ of flowing steam sterilizations are 30 minutes.
10) while hot sample being put into 0.01% methylene blue solution hunts leak.
11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 2 pharmaceutical composition injectable powder of the present invention
Prescription:
Prescription 1: injection NIUDAN
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Mannitol 800g
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 2: injection cattle three
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Mannitol 800g
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 3: injection Niu Hong
Taurine 3kg
Carthamus yellow 50g
Polyoxyethylene sorbitan monoleate 30g
PEG400 200ml
Mannitol 800g
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 4: injection Ox Mountain
Taurine 3kg
Folium Crataegi total flavones 50g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Mannitol 800g
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 5: injection cattle Pueraria lobota
Taurine 3kg
Puerarin 200g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Mannitol 800g
Water for injection adds to 10000ml
Prepare 1000 altogether
Prescription 6: injection Niu Hong
Taurine 3kg
Breviscapine 5g
Polyoxyethylene sorbitan monoleate 40g
PEG400 300ml
Mannitol 800g
Water for injection adds to 10000ml
Prepare 1000 altogether
Preparation technology:
1) vessel of at first dosing being used and antibiotic glass bottle, plug etc. carry out aseptic process.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) get polyoxyethylene sorbitan monoleate and make 20% water for injection, add the taurine, sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) of recipe quantity, the heated and stirred dissolving fully; PEG400 adds the water for injection of dosing amount 50%, adds the dissolving of taurine heated and stirred again, both mixings; Add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose.
4) needle-use activated carbon of adding dosing amount 0.05%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.22 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-40 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 25 hours was warming up to 25 ℃ of vacuum dryings 5 hours then.
9) lyophilizing finishes, and lid is rolled in tamponade.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 3 pharmaceutical composition sodium chloride transfusions of the present invention
Prescription:
Prescription 1: NIUDAN sodium chloride injection
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Sodium chloride 4500g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 2: cattle tri-chlorination sodium injection
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Sodium chloride 4500g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 3: the red sodium chloride injection of cattle
Taurine 3kg
Carthamus yellow 50g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Sodium chloride 4500g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 4: Ox Mountain sodium chloride injection
Taurine 3kg
Folium Crataegi total flavones 50g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Sodium chloride 4500g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 5: cattle Pueraria lobota sodium chloride injection
Taurine 3kg
Puerarin 200g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Sodium chloride 4500g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 6: cattle lamp sodium chloride injection
Taurine 3kg
Breviscapine 5g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Sodium chloride 4500g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Preparation technology:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get polyoxyethylene sorbitan monoleate and make 20% water for injection, add the taurine, sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) of recipe quantity, the heated and stirred dissolving fully; PEG400 adds the water for injection of dosing amount 50%, adds the dissolving of taurine heated and stirred again, both mixings; Sodium chloride is complete with the water for injection dissolving of dosing amount 40%.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.05%, heated and stirred 15 minutes.
5) filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4 pharmaceutical composition glucose infusion liquids of the present invention
Prescription:
Prescription 1: NIUDAN sodium chloride injection
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Glucose 25000g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 2: cattle tri-chlorination sodium injection
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Glucose 25000g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 3: the red sodium chloride injection of cattle
Taurine 3kg
Carthamus yellow 50g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Glucose 25000g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 4: Ox Mountain sodium chloride injection
Taurine 3kg
Folium Crataegi total flavones 50g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Glucose 25000g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 5: cattle Pueraria lobota sodium chloride injection
Taurine 3kg
Puerarin 200g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Glucose 25000g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Prescription 6: cattle lamp sodium chloride injection
Taurine 3kg
Breviscapine 5g
Polyoxyethylene sorbitan monoleate 50g
PEG400 400ml
Glucose 25000g
Water for injection adds to 500000ml
Prepare 1000 bottles altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get polyoxyethylene sorbitan monoleate and make 20% water for injection, add the taurine, sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) of recipe quantity, the heated and stirred dissolving fully; PEG400 adds the water for injection of dosing amount 50%, adds the dissolving of taurine heated and stirred again, both mixings; Glucose is complete with the water for injection dissolving of dosing amount 40%.
3) merge above-mentioned solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.05%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45 μ m.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5 pharmaceutical composition tablets of the present invention
Prescription:
Prescription 1: NIUDAN sheet
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Pregelatinized Starch 500g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Carboxymethylstach sodium 120g
Prepare 6000 altogether
Prescription 2: three of cattle
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Pregelatinized Starch 500g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Carboxymethylstach sodium 120g
Prepare 6000 altogether
Prescription 3: red of cattle
Taurine 3kg
Carthamus yellow 50g
Pregelatinized Starch 500g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Carboxymethylstach sodium 120g
Prepare 6000 altogether
Prescription 4: Ox Mountain sheet
Taurine 3kg
Folium Crataegi total flavones 50g
Pregelatinized Starch 500g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Carboxymethylstach sodium 120g
Prepare 6000 altogether
Prescription 5: cattle Pueraria lobota sheet
Taurine 3kg
Puerarin 200g
Pregelatinized Starch 500g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Carboxymethylstach sodium 120g
Prepare 6000 altogether
Prescription 6: cattle lamp sheet
Taurine 3kg
Breviscapine 5g
Pregelatinized Starch 500g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Carboxymethylstach sodium 120g
Prepare 6000 altogether
Preparation technology:
(1) it is standby taurine and sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution made soluble in water is standby.
(4) with taurine and sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine), pregelatinized Starch, microcrystalline Cellulose mix homogeneously; it is an amount of to add the 2%HPMC aqueous solution; stir, make suitable soft material.
(5) cross 20 mesh sieve system granules.
(6) granule is dried under 60 ℃ condition.
(7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
(8) sampling, the semi-finished product chemical examination.
(9) the sheet weight sheet of determining according to chemical examination.
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 medicament composition capsule agent of the present invention
Prescription:
Prescription 1: NIUDAN capsule
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Pregelatinized Starch 400g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Prepare 6000 altogether
Prescription 2: cattle three capsules
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Pregelatinized Starch 400g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Prepare 6000 altogether
Prescription 3: the red capsule of cattle
Taurine 3kg
Carthamus yellow 50g
Pregelatinized Starch 400g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Prepare 6000 altogether
Prescription 4: Ox Mountain capsule
Taurine 3kg
Folium Crataegi total flavones 50g
Pregelatinized Starch 400g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Prepare 6000 altogether
Prescription 5: cattle Pueraria lobota capsule
Taurine 3kg
Puerarin 200g
Pregelatinized Starch 400g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Prepare 6000 altogether
Prescription 6: cattle lamp capsule
Taurine 3kg
Breviscapine 5g
Pregelatinized Starch 400g
Microcrystalline Cellulose 100g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 40g
Prepare 6000 altogether
Preparation technology:
(1) it is standby taurine and sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution made soluble in water is standby.
(4) with taurine, sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine), pregelatinized Starch, microcrystalline Cellulose mix homogeneously; it is an amount of to add the 2%HPMC aqueous solution; stir, make suitable soft material.
(5) cross 18 mesh sieve system granules.
(6) granule is dried under 60 ℃ condition.
(7) dry good granule adds magnesium stearate, crosses 16 mesh sieve granulate, mix homogeneously.
(8) sampling, the semi-finished product chemical examination.
(9) loading amount of determining according to chemical examination incapsulates.
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7 medicament composition granule agent of the present invention
Prescription:
Prescription 1: NIUDAN granule
Taurine 3kg
Sodium tanshinone IIA sulfate 10g
Steviosin 50g
Citric acid 500g
Icing Sugar 20kg
The 2%HPMC50% alcoholic solution is an amount of
Prepare 10000 bags altogether
Prescription 2: cattle three granules
Taurine 3kg
Radix Notoginseng total arasaponins 100g
Steviosin 50g
Citric acid 500g
Icing Sugar 20kg
The 2%HPMC50% alcoholic solution is an amount of
Prepare 10000 bags altogether
Prescription 3: the red granule of cattle
Taurine 3kg
Carthamus yellow 50g
Steviosin 50g
Citric acid 500g
Icing Sugar 20kg
The 2%HPMC50% alcoholic solution is an amount of
Prepare 10000 bags altogether
Prescription 4: Ox Mountain granule
Taurine 3kg
Folium Crataegi total flavones 50g
Steviosin 50g
Citric acid 500g
Icing Sugar 20kg
The 2%HPMC50% alcoholic solution is an amount of
Prepare 10000 bags altogether
Prescription 5: cattle Puerariae granule
Taurine 3kg
Puerarin 200g
Steviosin 50g
Citric acid 500g
Icing Sugar 20kg
The 2%HPMC50% alcoholic solution is an amount of
Prepare 10000 bags altogether
Prescription 6: cattle lamp granule
Taurine 3kg
Breviscapine 5g
Steviosin 50g
Citric acid 500g
Icing Sugar 20kg
The 2%HPMC50% alcoholic solution is an amount of
Prepare 10000 bags altogether
Preparation technology:
1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that taurine and sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) were pulverized 100 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) the method mix homogeneously that taurine, sodium tanshinone IIA sulfate (or Radix Notoginseng total arasaponins, Carthamus yellow, Folium Crataegi total flavones, puerarin, breviscapine) and steviosin, citric acid, Icing Sugar are progressively increased with equivalent; it is an amount of to add the 2%HPMC50% alcoholic solution; stir; make suitable soft material
4) cross 20 mesh sieve system granules.
5) granule is dried under 50 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.
8) packing, finished product is examined entirely, the packing warehouse-in.

Claims (5)

1. one kind is used to prepare the pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that the parts by weight of making the crude drug of this pharmaceutical composition consist of: 500～15000 parts of taurines, 2～50 parts of sodium tanshinone IIA sulfates.
2. pharmaceutical composition as claimed in claim 1 is characterized in that, the parts by weight of making the crude drug of this pharmaceutical composition consist of: 1500～6000 parts of taurines, 5～20 parts of sodium tanshinone IIA sulfates.
3. pharmaceutical composition as claimed in claim 2 is characterized in that, the parts by weight of making the crude drug of this pharmaceutical composition consist of: 3000 parts of taurines, 10 parts of sodium tanshinone IIA sulfates.
4. as each described pharmaceutical composition of claim 1-3, it is characterized in that this pharmaceutical composition can be made clinically any or pharmaceutically acceptable dosage form with mixing acceptable accessories.
5. pharmaceutical composition as claimed in claim 4 is characterized in that this pharmaceutical composition can be made injection or oral formulations.
CN2006100438986A 2006-04-29 2006-04-29 Taurine and medical combination for treating cardiovascular and cerebrovascular diseases Expired - Fee Related CN101062027B (en)

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CN100435803C (en) * 2006-06-07 2008-11-26 广州中医药大学 Use of taurine in preparation of injection containing puerarin
CN107261105A (en) * 2017-06-26 2017-10-20 郑相国 Treat the Chinese patent drug of cardiovascular and cerebrovascular disease
CN110237085A (en) * 2018-06-13 2019-09-17 武汉圣朗生物工程有限公司 Pharmaceutical preparation and application thereof

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