CN1745767A - Use of depot containing Chuanxiong against aspirin - Google Patents
Use of depot containing Chuanxiong against aspirin Download PDFInfo
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Abstract
A Chinese medicine in the form of injection containing Chuan-xiong rhizome for treating the aspirin-resistant cardiovascular disease is prepared from red sage root and Chuan-xiong rhizome.
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to the application of a kind of injection in preparation treatment resistant medication of aspirin.
Background technology
Aspirin (Aspirin) claim aspirin or aspirin again, is applied to clinical existing more than 80 year history, is a kind of ancient analgesic, analgesic.Along with the going deep into of prostaglandin research, aspirin there has been new understanding again in recent years: analgesic except being used for traditionally clinically, analgesia, the antiinflammatory, also be used for antiplatelet aggregation etc.Clinical trial shows that aspirin is the effective antiplatelet drug of cardiovascular and cerebrovascular disease high-risk patient primary prevention, and is also effective to the secondary prevention of myocardial infarction and ischemic vascular events.
But use the aspirin of therapeutic dose at present clinically, still there is part cardiovascular and cerebrovascular disease patient that coronary artery thrombus and apoplexy have taken place, strengthen therapeutic dose, not only fail to reach treatment and prevention purpose, and untoward reaction increases, this phenomenon be called " aspirin resistance " (Aspirin Resistance, AR).
Through long term follow-up, reason is as follows: first platelet is by other pathway activation, can not be blocked [Valles J by aspirin, Santos MT, Aznar J, et al.Erythrocyte Promotion of platelet reactivity decreases the effectivenessof aspirin as an antithrombotic therapeutic modality:the effect of low-dose aspirin is less thanoptimal in patients with vascular disease due to prothrombotic effects of erythrocytes on plateletreactivity.Circulation, 1998; 97:350-355]; The dosage that second some needs of patients is bigger than routine dose just can obtain best thromboembolism preventing effect, there is not evidence to show relevant [the Patrono C.Prevention ofmyocardial infarction and stroke by aspirin:different mechanisms of aspirin thromboembolism preventing effect with dosage? Different dosage? Thromb.Res., 1998; 92:S7-S12]; Although using the routine dose aspirin, the 3rd some patient also can generate TXA
2[Tayllor DW, Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy:arandomized controlled trail; ASA and Carotid Endarterectomy (ACE) Trial Collaborators.Lancet, 1999; 353:2179-2184].
Studies show that the generation of AR is relevant with following mechanism.
Erythrocyte improves platelet response
Platelet-erythrocyte interacts influence platelet response, synthesizes and platelet is raised and caused aspirin resistance by platelet release reaction, eicosanoids.Erythrocyte causes TXA
2Synthetic increasing, 5-HT, β-TG and ADP discharge, generation [the Valles J that shows erythrocyte adjusting platelet eicosanoids, et al.Erythrocyte metabolically enhancescollagen-induced platelet responsiveness via increased thromboxane production, adenosinediphosphate release, and recruitment.Blood, 1991; 78:154-162].
Arachidonic acid (PGF
2
) metabolism
Arachidonic acid produces a series of bioactive PGF that have through lipid peroxidation
2See complex.F
2-isoprostanes is the important new predictor of angiopathy.Unstable angina, stable angina pectoris, ariant angina patient and healthy people take aspirin 100mg/d and measure 8-iso-PGF
2(mark of matter fat peroxidation) and 11 dehydrogenations-TXA
2(TXA
2Studies show that biosynthetic mark), unstable angina patient 8-iso-PGF
2Urinary excretion is apparently higher than stablizing patient with angina pectoris and matched group; TXA
2Excretion apparently higher than stable patient with angina pectoris.Unstable angina patient's oxidant stress increases, 8-iso-PGF
2Increase, platelet is to the increased response of other agonist.
Smoking stimulates
Smoking is the cardiovascular disease principal risk factor.Data shows that aspirin can the anticoagulant rate reduce platelet aggregation [the Davis JW that causes, et al.Cigarette smoking-induced enhancement of platelet function:lack ifprevention by aspirin in men with coronary artery disease.J Lab Clin Med, 1982; 126:637-639].Platelet aggregation rate reduces after the smoking.Take aspirin before non-smoker and the smoking addiction person smoking and can prevent that platelet aggregation rate from descending.
The catecholamine levels platelet increasing is assembled to be increased
External platelet shows adrenergic sensitivity and has contact [Larsson PT et al between platelet activation that catecholamine causes and the acute coronary syndrome, Norepinephrine-induced human platelet activation in vivo is only partlycounteracted by aspirin.Circulation, 1994; 89:1951-1957].40 patients of acute myocardial infarction are divided into warfarin group and aspirin group at random.Get blood before and after the bicycle ergometor exercise, relatively two groups baseline characteristic, movement time and maximum heart rate.The warfarin group obviously reduces than aspirin group platelet aggregation rate when baseline, illustrates that aspirin has the effect of antiplatelet aggregation.Two groups platelet aggregation rate all reduces during motion, shows that the platelet aggregation ability increases.Its reason may be that the noradrenaline levels increase causes platelet activation.
Platelet increases the sensitivity of collagen
Collagen is the agonist of physiological important platelet aggregation.Two experimental study aspirin reply and collagen between relation.Before aspirin 324mg/kg is taken in a test (n=8 healthy male), measure the bleeding time after taking medicine 2 hours, distinguish aspirin respondent and nonresponder.87 of philtrums have participated in second test, give collagen 0.15-4 μ g/ml and determine aspirin respondent and the nonresponder's platelet sensitivity to collagen.Among 8 patients of first test, 5 aspirin respondents, 3 nonresponders.Aspirin respondent and the nonresponder preceding bleeding time indifference [(408 ± 121) and (330 ± 30) second, P＞0.05] of taking medicine has significant difference [(720 ± 225) and (330 ± 52) second] after taking medicine.Among 7 patients of second test, 4 aspirin respondents, 3 nonresponders.Aspirin respondent and the nonresponder preceding bleeding time indifference [(405 ± 52) and (357 ± 31) second of taking medicine, P＞0.05], significant difference [(623 ± 189) and (345 ± 54) second] [Kawasaki T is arranged after taking medicine, el at.Incresed platelet sensitivity to cllagen in individuals resistant to low aspirin.Stroke, 2000; 31:591-595].
Cycloxygenase-2 (COX-2) (p900)
Cox is the synthetic rate-limiting enzyme of prostaglandin.Cox-1 expresses in most cells and tissue.In the great majority tissue, can not detect under the mRNA of Cox-2 and the protein normal condition.[Weber AA, et al.Cyclooxygenase-2 in human platelet as a possible factor in aspirin resistance.Lancet, 1993 such as nearest Webr; 353:900] report that protein and the mRNA of Cox-2 express in healthy people's circulation platelet, this may be a reason of aspirin resistance.
Drug interaction
The interaction of aspirin and other nonsteroidal anti inflammatory medicines (NSAIDS) can weaken aspirin to hematoblastic effect.Aspirin needs at first to combine lysine-the 120th, the coefficient site of all NSAIDS with lysine-120 to the acetylation of serine residue.NSAIDS is stronger to the affinity of lysine-120, thereby has stoped the inhibitory action of aspirin to platelet Cox-1.
More than set forth possible mechanisms of aspirin resistance.Clear and definite platelet activation mechanism and reversible risk factor help to reduce the generation of aspirin resistance, improve patient's prognosis.
The said aspirin resistance of the present invention can not effectively stop thromboxane A after being meant and taking aspirin
2Synthetic, promptly aspirin has lost the protective effect to cardio-cerebrovascular, this phenomenon is referred to as aspirin resistance.Concerning Most patients, aspirin can make cardiovascular danger reduce by 25%, but the patient of aspirin resistance uses the aspirin for treatment cardiovascular disease, can not prevent the generation of cardiovascular event, can increase the incidence rate of heart infarction and apoplexy on the contrary, these find the use of restriction aspirin.Therefore, these cardiovascular disease are referred to as aspirin repellency cardiovascular disease in the middle of the present invention, particularly refer to coronary heart disease, the angina pectoris of using aspirin for treatment invalid.The present invention will be referred to as the medicine of anti-aspirin resistance to the medicine that aspirin repellency cardiovascular disease has a therapeutical effect, and this therapeutical effect is referred to as anti-aspirin resistance effect.
At present, the report for the treatment aspirin resistance also is not a lot.[Effects of pretreatment withclopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneouscoronary intervention:the PCI-CURE study.Lancet, 2001] such as Yusuf S have been reported to add on the basis of aspirin for treatment and have been adjoined Gray with chlorine and can reduce the incidence rate that Acute Coronary Syndrome Patients comprises the early stage and secular serious cardiovascular incident of patient of percutaneous coronary intervention (pci).
The Chinese medicine blood-regulating drug, particularly the blood-activating stasis-removing kind medicine is the medicine that ancient Chinese medicine doctor is used always, this class medicine has the effect of promoting blood flow to regulate menstruation, removing blood stasis Xiao Disorder, blood-activating analgetic, detumescence and promoting granulation, modern pharmacology confirms, blood-regulating drug has the expansion coronary artery, increases coronary flow, reduce myocardial oxygen consumption, reduce peripheral vascular resistance, anticoagulant, microcirculation improvement, suppress thrombosis, fortifying fibre protein dissolution activity, anticoagulation system, microcirculation improvement, effects such as smooth muscle spasm are alleviated in blood pressure lowering.The clinical effect of Rhizoma Chuanxiong in the blood-regulating drug, Radix Salviae Miltiorrhizae, Herba Leonuri, Semen Persicae, Flos Carthami, Hirudo etc. is constantly expanded, and particularly the research of Radix Salviae Miltiorrhizae is particularly outstanding.
Find that through secular clinical research the traditional Chinese medical science thinks that the etiology and pathology of coronary heart disease is many because " imbalance of YIN and YANG, mechanism of qi be contrary to cause disorderly that the painstaking effort stasis of blood stagnates, blockage of the cardiac vessels, stagnation of QI and blood may bring about pain ".According to mentioned above principle, the someone has chosen Radix Salviae Miltiorrhizae, and Rhizoma Chuanxiong is that raw material is made preparation, and said preparation has the effect of blood circulation promoting and blood stasis dispelling, is used for the angina pectoris that the coronary disease disease causes.Because its determined curative effect, untoward reaction is few, is clinical treatment coronary heart disease, uncomfortable in chest, anginal Chinese patent medicine commonly used.At present the research of said preparation is mainly concentrated in the research of the angina pectoris that the coronary disease disease causes, the effect of relevant said preparation treatment aspirin resistance does not appear in the newspapers as yet.In order to alleviate the phenomenon that can produce aspirin resistance when cardio-cerebral vascular disease patient uses aspirin Drug therapy cardiovascular and cerebrovascular disease, some researchers are being sought the medicine that can substitute or alleviate the aspirin resistance phenomenon at present, the present invention tests at present more present medicines just on this basis, in the hope of finding its new medicine use, easily produce the aspirin resistance phenomenon to solve present aspirin medication.
Summary of the invention
The object of the present invention is to provide the application of a kind of pharmaceutical composition in the medicine of the anti-aspirin resistance of preparation.
Described Chinese medicine composition is by comprising that following crude drug makes: Radix Salviae Miltiorrhizae 1～99%, Rhizoma Chuanxiong 1～99%. Preferred described Chinese medicine composition is by comprising that following crude drug makes: Radix Salviae Miltiorrhizae 20～80%, Rhizoma Chuanxiong 20～80%; Best described Chinese medicine composition is by comprising that following crude drug makes: Radix Salviae Miltiorrhizae 50%, Rhizoma Chuanxiong 50%.
Described Chinese medicine composition can be made any form on the pharmaceutics, as injection, oral formulations form; Wherein injection comprises injection, drip liquid, injectable powder; Oral formulations comprises granule, capsule, tablet, electuary, powder, oral liquid formulations form.
The preparation of the effective ingredient of described Chinese medicine composition can be adopted following method: water extraction, decoction and alcohol sedimentation technique, extraction, infusion process, percolation, reflux extraction, continuous backflow extraction method, macroreticular resin absorbing method preparation.For example, these crude drug pulverize mix homogeneously can be made powder takes after mixing it with water; Also can be with these medicines decocting together, the condensed water decocting liquid is made oral liquid then.
Injection of the present invention can adopt following method preparation, but this can not limit protection scope of the present invention.
Get Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, decoct with water three times, collecting decoction filters, and filtrate concentrates, and handles secondary with ethanol precipitation, adds behind the ethanol all cold preservation at every turn and places, and filters, and merging filtrate concentrates, and with the water for injection dilution, regulates pH value with dilute hydrochloric acid; Cold preservation filters, and regulates pH value with sodium hydroxide solution, concentrates l, and cold preservation filters, and the re-adjustment pH value boils, and adds active carbon, filters, and filtrate is regulated pH value, adds the injection water, embedding, and sterilization, promptly.
Best injection of the present invention can adopt following method preparation:
Get Radix Salviae Miltiorrhizae 2000g, Rhizoma Chuanxiong 2000g is standby
More than two flavors, decoct with water 2 hours for the first time three times, second and third time each 1.5 hours, collecting decoction filters, filtrate is concentrated into about 2000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 75%, be 85% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 10% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 30 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.
In order to understand essence of the present invention better,, its new purposes in pharmaceutical field is described below by the result of the test of this pharmaceutical composition of clinical observation at anti-" aspirin resistance ".
The present invention adopts the research method to aspirin resistance commonly used at present, by measuring platelet aggregation rate, judge whether the patient has the effect that reduces aspirin resistance after taking medicine of the present invention, the present invention passes through clinical research observation, proved the application of medicine of the present invention in the medicine of the anti-aspirin resistance of preparation, medicine of the present invention has the effect of anti-aspirin resistance, in order to understand the present invention better, clinical test results with medicine of the present invention illustrates its new purposes in pharmaceutical field below, be convenient narration, below medicine of the present invention be called GUANXINNING ZHUSHEYE.
Experimental example GUANXINNING ZHUSHEYE (preparing gained according to embodiment 1 preparation method) reduces aspirin resistance effect experiment
We carry out aspirin to 20 Yu Jia cadre's sanitarium retired cadres and family members under the Beijing Military Area Command and detect examination, filter out 86 of aspirin resistance patients (50 of men altogether, 36 of woman, 72.5 ± 12.1 years old age), find that the aspirin resistance incidence rate is about 15.6%.The aspirin resistance patient is divided into (55 of combination group; Unite and use aspirin and coronary disease injection for curing), single with GUANXINNING ZHUSHEYE (31, the aspirin of stopping using, single GUANXINNING ZHUSHEYE of using), measure the platelet maximum agglutination rate once more after treating for 2 weeks.
Method:
One. inclusion criteria
1. take low-dosage aspirin continuously and surpass 2 all persons
2. use U.S. CHRON-LOG AGGREGOMETER 540VS and detect the platelet maximum agglutination rate of its arachidonic acid-induction greater than 30%
Meeting above-mentioned two persons simultaneously can be selected in
Two. exclusion standard:
1. disease in the blood system hemorrhage especially;
2. cancer
3. chronic obstructive pulmonary disease
The person promptly is excluded to meet the one
Three. grouping:
Combination group: select 55 aspirin resistance patients at random, continue to use aspirin, add simultaneously with 2 all GUANXINNING ZHUSHEYE, 20-40ml adds in 5% glucose injection, and quiet, once-a-day.
List is used the GUANXINNING ZHUSHEYE group: select 31 aspirin resistance patients at random, the aspirin of stopping using is used GUANXINNING ZHUSHEYE instead, and 20-40ml adds in 5% glucose injection, and quiet, once-a-day, 2 weeks.
Four. curative effect determinate standard
Produce effects: the platelet maximum agglutination rate is less than 30% (effect is equal to normal aspirin effect)
Effectively: the platelet maximum agglutination rate is greater than 30%, but is lower than for 80% (the platelet activation value normally suppresses effect but be lower than aspirin in normal range)
Invalid: the maximum agglutination rate excursion is ± 10% before and after the treatment
Raise: maximum agglutination rate changes greater than 10% before and after the treatment
Effective percentage=(produce effects number+effective number)/total number of persons
The result
One, aspirin resistance aspirin and GUANXINNING ZHUSHEYE are united use
1. treatment effective percentage
| Therapeutic effect | Number | Ratio % |
| The produce effects enabledisable raises | 39 7 5 4 | 71 13 9 7 |
The total effective rate that aspirin and GUANXINNING ZHUSHEYE are united use reaches 84% (46/55)
2. compare before and after the platelet maximum agglutination rate:
Before the treatment (65.9 ± 23.7), treatment 2 week backs (28.9 ± 20.5) are through paired t-test: p＜0.01; The average range of decrease of platelet aggregation rate is 51.8%.
Annotate: value before reduction amplitude=(being worth after value-medication before the medication)/medication
Two. aspirin resistance stops aspirin, singly uses GUANXINNING ZHUSHEYE
1. treatment effective percentage
| Therapeutic effect | Number | Ratio % |
| The produce effects enabledisable raises | 10 6 7 8 | 32 19 23 26 |
Stop aspirin, single GUANXINNING ZHUSHEYE of using, the total effective rate that aspirin resistance is treated reaches 51% (16/31)
2. compare before and after the platelet maximum agglutination rate:
Before the treatment (80.3 ± 25.7), treatment 2 week backs (59.1 ± 29.2) are through paired t-test: p＜0.05; The average range of decrease of platelet aggregation rate is 18.9%.
Annotate: value before reduction amplitude=(being worth after value-medication before the medication)/medication
Conclusion: to the aspirin resistance person, use the treatment of aspirin and GUANXINNING ZHUSHEYE can obviously lower platelet aggregation rate simultaneously, effective percentage is 84%, and the average range of decrease is 51.8%; List is treated aspirin resistance with GUANXINNING ZHUSHEYE, and its effective percentage is 51%, and the average range of decrease is 18.9%.Presentation of results is to the invalid cardiovascular patient of independent use aspirin for treatment, GUANXINNING ZHUSHEYE and aspirin share has the effect of good curing aspirin resistance, use GUANXINNING ZHUSHEYE treatment aspirin resistance that effect is preferably also arranged separately, but the effect not as good as with the aspirin combination group, whether GUANXINNING ZHUSHEYE reduces aspirin resistance by other mechanism of action, the further research of still needing.
The specific embodiment
Embodiment 1:
Get Radix Salviae Miltiorrhizae 2000g, Rhizoma Chuanxiong 2000g is standby
More than two flavors, decoct with water 2 hours for the first time three times, second and third time each 1.5 hours, collecting decoction filters, filtrate is concentrated into about 2000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 75%, be 85% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 10% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 30 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
Embodiment 2:
Get Radix Salviae Miltiorrhizae 300g, Rhizoma Chuanxiong 3000g is standby
More than two flavors, decoct with water 3 hours for the first time three times, second and third time each 2 hours, collecting decoction filters, filtrate is concentrated into about 1500ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 70%, be 80% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 3000ml, regulate pH value to 3.5 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 8% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 35 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
Embodiment 3:
Get Radix Salviae Miltiorrhizae 3500g, Rhizoma Chuanxiong 500g is standby
More than two flavors, decoct with water 2.5 hours for the first time three times, second and third time each 1.5 hours, collecting decoction filters, filtrate is concentrated into about 3000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 80%, be 85% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 10% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 30 minutes, added active carbon 0.15%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
Embodiment 4:
Get Radix Salviae Miltiorrhizae 50g, Rhizoma Chuanxiong 5000g is standby
More than two flavors, decoct with water 4 hours for the first time three times, second and third time each 1.5 hours, collecting decoction filters, filtrate is concentrated into about 2000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 85%, be 80% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 12% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 30 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
Embodiment 5:
Get Radix Salviae Miltiorrhizae 100g, Rhizoma Chuanxiong 4000g is standby
More than two flavors, decoct with water 2 hours for the first time three times, second and third time each 1.5 hours, collecting decoction filters, filtrate is concentrated into about 2000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 85%, be 80% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 12% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 30 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1200ml, embedding, sterilization, promptly.
Embodiment 6:
Get Radix Salviae Miltiorrhizae 3000g, Rhizoma Chuanxiong 1000g is standby
More than two flavors, decoct with water 4 hours for the first time three times, second and third time each 3.5 hours, collecting decoction filters, filtrate is concentrated into about 2000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 85%, be 80% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 10% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 25 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
Embodiment 7
Get Radix Salviae Miltiorrhizae 2500g, Rhizoma Chuanxiong 1500g, decoct with water three times, each 2 hours, collecting decoction, filter, filtrate is concentrated into 3000ml, and the ethanol precipitation with 85% is handled secondary, equal cold preservation is placed after adding ethanol at every turn, filter, merging filtrate is concentrated into 1000ml, be diluted to 3500ml with water for injection, regulate pH value to 3.0～3.6 with dilute hydrochloric acid; Cold preservation filters, and regulates pH value to 6.0～6.9 with sodium hydroxide solution, is concentrated into 1200ml, cold preservation, filter, boil re-adjustment pH value to 6.0～6.9, adds active carbon, filters, filtrate is regulated pH value to 6.0～6.9, adds injection water 1200ml, embedding, and sterilization, promptly.
Embodiment 8
Get Radix Salviae Miltiorrhizae 2500g, Rhizoma Chuanxiong 1500g, decoct with water three times, each 2 hours, collecting decoction filtered, and filtrate is concentrated into 3000ml, embedding, and sterilization is made oral liquid, promptly.
Embodiment 9
Get Radix Salviae Miltiorrhizae 200g, Rhizoma Chuanxiong 100g, decoct with water three times, each 3 hours, collecting decoction filtered, and filtrate is concentrated into 300ml, adds appropriate amount of auxiliary materials, and drying is made granule, promptly.
Embodiment 10
Get Radix Salviae Miltiorrhizae 500g, Rhizoma Chuanxiong 500g, decoct with water three times, each 1 hour, collecting decoction filtered, and filtrate is concentrated into 200ml, adds appropriate amount of auxiliary materials, and drying is made granule, incapsulates, promptly.
Embodiment 10
Get Radix Salviae Miltiorrhizae 200g, Rhizoma Chuanxiong 2000g, decoct with water three times, each 4 hours, collecting decoction filtered, and filtrate is concentrated into 1000ml, adds appropriate amount of auxiliary materials, and drying is made granule, tabletting, promptly.
Claims (10)
1, the application of a kind of pharmaceutical composition in the low anti-medicine of the anti-aspirin of preparation, wherein this drug composition is by comprising that following crude drug makes: Radix Salviae Miltiorrhizae 1～99%, Rhizoma Chuanxiong 1～99%.
2, application as claimed in claim 1, wherein this drug composition is by comprising that following crude drug makes: Radix Salviae Miltiorrhizae 20～80%, Rhizoma Chuanxiong 20～80%.
3, application as claimed in claim 1, wherein this drug composition is by comprising that following crude drug makes: Radix Salviae Miltiorrhizae 50%, Rhizoma Chuanxiong 50%.
4,, it is characterized in that described compositions is a kind of of injection, oral formulations form as any one described application in the claim 1～3.
5, application as claimed in claim 4 is characterized in that described compositions is an injection.
6, application as claimed in claim 5 is characterized in that described pharmaceutical composition prepares with following method:
Get Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, decoct with water three times, collecting decoction filters, and filtrate concentrates, and handles secondary with ethanol precipitation, adds behind the ethanol all cold preservation at every turn and places, and filters, and merging filtrate concentrates, and with the water for injection dilution, regulates pH value with dilute hydrochloric acid; Cold preservation filters, and regulates pH value with sodium hydroxide solution, concentrates 1, and cold preservation filters, and the re-adjustment pH value boils, and adds active carbon, filters, and filtrate is regulated pH value, adds the injection water, embedding, and sterilization, promptly.
7, application as claimed in claim 6 is characterized in that described pharmaceutical composition prepares with following method:
Get Radix Salviae Miltiorrhizae 2000g, Rhizoma Chuanxiong 2000g, decoct with water three times, 2 hours for the first time, second and third time each 1.5 hours, collecting decoction filters, filtrate is concentrated into about 2000ml, handles secondary with ethanol precipitation, makes for the first time to contain the alcohol amount and reach 75%, be 85% for the second time, add behind the ethanol all cold preservation at every turn and place, filter, merging filtrate, be concentrated into about 700ml, be diluted to 4000ml, regulate pH value to 3.2 with dilute hydrochloric acid with water for injection; Cold preservation filters, and regulates pH value to 6.8 with 10% sodium hydroxide solution, is concentrated into 1000ml, and cold preservation filters, re-adjustment pH value to 6.8 boiled 30 minutes, added active carbon 0.2%, and is cold slightly, filters, filtrate is regulated pH value to 6.8, and add the injection water and make into 1000ml, embedding, sterilization, promptly.
8,, it is characterized in that the application of this pharmaceutical composition in the medicine of preparation treatment aspirin repellency cardiovascular and cerebrovascular disease as any one described application in the claim 1～3.
9, application as claimed in claim 8 is characterized in that said aspirin repellency cardiovascular and cerebrovascular disease is meant the invalid cardiovascular and cerebrovascular disease of use aspirin for treatment.
10, application as claimed in claim 9 is characterized in that said aspirin repellency cardiovascular and cerebrovascular disease is meant invalid coronary heart disease, the angina pectoris of use aspirin for treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410071863 CN1745767A (en) | 2004-09-07 | 2004-09-07 | Use of depot containing Chuanxiong against aspirin |
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| CN 200410071863 CN1745767A (en) | 2004-09-07 | 2004-09-07 | Use of depot containing Chuanxiong against aspirin |
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| CN1745767A true CN1745767A (en) | 2006-03-15 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2024113586A1 (en) * | 2022-11-29 | 2024-06-06 | 神威药业集团有限公司 | Method for preparing guanxinning composition |
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2004
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024113586A1 (en) * | 2022-11-29 | 2024-06-06 | 神威药业集团有限公司 | Method for preparing guanxinning composition |
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