CN1714827A - Use of medicine in preparing medicine for treating anti-aspirin - Google Patents
Use of medicine in preparing medicine for treating anti-aspirin Download PDFInfo
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- CN1714827A CN1714827A CN 200410019846 CN200410019846A CN1714827A CN 1714827 A CN1714827 A CN 1714827A CN 200410019846 CN200410019846 CN 200410019846 CN 200410019846 A CN200410019846 A CN 200410019846A CN 1714827 A CN1714827 A CN 1714827A
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides the new use of a kind of medicine composition. The medicine composition consists of red sage and supplementary material. Clinical test shows that the medicine composition has the property of improving aspirin resistance and may be used in treating aspirin resistance cardiac vascular diseases to raise the life quality of the aspirin resistance cardiac vascular disease patient.
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to the application of a kind of medicine 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 ll dehydrogenation-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.
Aspirin resistance 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, it is raw material that the someone has chosen Radix Salviae Miltiorrhizae, makes preparation with citric acid, essence, sucrose, 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.
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.
Following drug component of the present invention is formed, consumption all has the low anti-curative effect of anti-preferably aspirin: Radix Salviae Miltiorrhizae and adjuvant; Wherein adjuvant comprises sucrose; Preferred adjuvant comprises sucrose, citric acid; Best adjuvant comprises sucrose, citric acid, essence.
Find that in experiment each component of medicine of the present invention all has the low anti-curative effect of anti-preferably aspirin in following dosage: get Radix Salviae Miltiorrhizae 500～1500g, citric acid 5～15g, essence 1.5～4.5ml, sucrose 450～1800g; Preferred each amounts of components is Radix Salviae Miltiorrhizae 1000g, citric acid 10g, essence 3ml, sucrose 900g.
The preparation of effective ingredient of the present invention 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; But, preferably adopt following technology to extract, but this can not limit protection scope of the present invention to raw material in order to make each crude drug of this medicine bring into play drug effect better.
Get Radix Salviae Miltiorrhizae 1000g, citric acid 10g, essence 3ml, sucrose 900g are standby;
Get Radix Salviae Miltiorrhizae 1000g and decoct with water three times, 2 hours for the first time, second and third time each 1.5 hours, collecting decoction filters, and filtrate is concentrated into 500ml, add equivalent ethanol, fully stir, left standstill 12 hours, get supernatant, reclaim ethanol, being concentrated into relative density is the thick paste of 1.30～1.40 (50～60 ℃), add citric acid, essence and sucrose, make granule, drying, promptly.
Medicine of the present invention can be made granule, capsule, tablet, electuary, powder, oral liquid formulations form.
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, uses immune enzyme linked immunosorbent assay mensuration patient urine sample is provided, and is used for analyzing 11-dehydrogenation thromboxance B
2(TXB
2) variation of level, 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, and in order to understand the present invention better, the 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 DANSHEN KELI.
The experimental example DANSHEN KELI reduces aspirin resistance effect experiment
Retrospective approach is adopted in this research: normal value with reference to Australia about the aspirin resistance result of study
Physical data
This is organized 90 routine patients and is selected from the outpatient, and is the cardiovascular patient that has the aspirin resistance tendency through measuring.Male 55 people wherein, women 35 people.70 years old～85 years old age, 77 years old mean age.Clothes aspirin person 30 people; Take DANSHEN KELI 30 people; Sharer 30 people (all patient took medicine more than half a year at least continuously to the day of sampling).
Materials and methods
Institute's urine sample of adopting is urina sanguinis stage casing for the first time, drop into immediately after getting in the liquid nitrogen, after be stored in-86 ℃ of cryogenic refrigerators standby.Use immune enzyme linked immunosorbent assay and detect 11-dehydrogenation TXB
2, test kit adopts Cayman Chemical company product, and all experiment is finished in the biological institute of sky scholar's power academy, and patient's packet conditions is carried out double blinding to lab assistant and later data statistician.
The result
As shown in table 1.
Table 1. is respectively organized patient's urine value 11-dehydrogenation TXB
2(ng/mmol) X ± SD
| Aspirin (n=30 example) | DANSHEN KELI (n=30 example) | Aspirin and DANSHEN KELI are share (n=30 example) |
| Urine value 11-dehydrogenation TXB 2(ng/mmol) | Urine value 11-dehydrogenation TXB 2(ng/mmol) | Urine value 11-dehydrogenation TXB 2(ng/mmol) |
| 26.17±10.54 | 21.48±9.93 | 20.10±9.07 |
Conclusion: DANSHEN KELI is share between aspirin group and aspirin use group separately group has obvious significant difference, p＜0.05 between the TXB2 excretion in the urine; No obvious significant difference between the TXB2 excretion in urinating between DANSHEN KELI group and aspirin group group, p＞0.05; No obvious significant difference between the TXB2 excretion during DANSHEN KELI group and DANSHEN KELI are share and urinated between aspirin group group, p＞0.05.
This experimental result proves that DANSHEN KELI is share aspirin can make the TXB2 excretion in the urine reduce thromboxane A promptly capable of blocking in vivo
2(TXA
2) formation, reduce hematoblastic sticking and blood coagulation, thereby anticoagulant, reduce the generation of arteriosclerosis, myocardial infarction, the presentation of results DANSHEN KELI has anti-aspirin resistance effect, the cardiovascular patient invalid to aspirin, DANSHEN KELI still has the effect that improves life index.Whether this medicine reduces aspirin resistance by other mechanism of action, the further research of still needing.
Medicine of the present invention is to be prepared from by following examples, and following specific embodiment is an explanation of the invention, can not limit the present invention.
The specific embodiment
Embodiment 1: the preparation method of DANSHEN KELI
Get Radix Salviae Miltiorrhizae 1000g, citric acid 10g, essence 3ml, sucrose 900g are standby;
Get Radix Salviae Miltiorrhizae 1000g and decoct with water three times, 2 hours for the first time, second and third time each 1.5 hours, collecting decoction filters, and filtrate is concentrated into 500ml, add equivalent ethanol, fully stir, left standstill 12 hours, get supernatant, reclaim ethanol, being concentrated into relative density is the thick paste of 1.30～1.40 (50～60 ℃), add citric acid, essence and sucrose, make granule, drying, promptly.
Embodiment 2: the preparation method of DANSHEN KELI
Radix Salviae Miltiorrhizae 500g, citric acid 5g, essence 4.5ml, sucrose 450g are standby;
Get Radix Salviae Miltiorrhizae 500g and decoct with water three times, 2 hours for the first time, second and third time each 1.5 hours, collecting decoction filters, and filtrate is concentrated into 500ml, add equivalent ethanol, fully stir, left standstill 12 hours, get supernatant, reclaim ethanol, being concentrated into relative density is the thick paste of 1.30～1.40 (50～60 ℃), add citric acid, essence and sucrose, make granule, drying, promptly.
Embodiment 3: the preparation method of DANSHEN KELI
Get Radix Salviae Miltiorrhizae 1500g, citric acid 15g, essence 1.5ml, sucrose 900g are standby;
Get Radix Salviae Miltiorrhizae 1500g and decoct with water three times, 2 hours for the first time, second and third time each 1.5 hours, collecting decoction filters, and filtrate is concentrated into 500ml, add equivalent ethanol, fully stir, left standstill 12 hours, get supernatant, reclaim ethanol, being concentrated into relative density is the thick paste of 1.30～1.40 (50～60 ℃), add citric acid, essence and sucrose, make granule, drying, promptly.
Embodiment 4: the preparation method of DANSHEN KELI
Get Radix Salviae Miltiorrhizae 800g, citric acid 7g, essence 3ml, sucrose 700g are standby;
Get Radix Salviae Miltiorrhizae 800g and decoct with water three times, 2 hours for the first time, second and third time each 1.5 hours, collecting decoction filters, and filtrate is concentrated into 500ml, add equivalent ethanol, fully stir, left standstill 12 hours, get supernatant, reclaim ethanol, being concentrated into relative density is the thick paste of 1.30～1.40 (50～60 ℃), add citric acid, essence and sucrose, make granule, drying, promptly.
Claims (9)
1, the application of a kind of pharmaceutical composition in the low medicine that resists of the anti-aspirin of preparation, wherein the composition of said composition comprises: Radix Salviae Miltiorrhizae and sucrose.
2, application as claimed in claim 1, wherein the used adjuvant of said composition can also comprise citric acid.
3, application as claimed in claim 2, wherein the used adjuvant of said composition can also comprise essence.
4, application as claimed in claim 3, wherein the consumption proportion of each component is to get Radix Salviae Miltiorrhizae 500～1500g, citric acid 5～15g, essence 1.5～4.5ml, sucrose 450～1800g.
5, application as claimed in claim 4, wherein the consumption proportion of each component is to get Radix Salviae Miltiorrhizae 1000g, citric acid 10g, essence 3ml, sucrose 900g.
6,, it is characterized in that described compositions is a kind of of granule, capsule, tablet, electuary, powder, oral liquid formulations form as any one described application in the claim 1～5.
7,, 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 1～5.
8, application as claimed in claim 7 is characterized in that said aspirin repellency cardiovascular and cerebrovascular disease is meant the invalid cardiovascular and cerebrovascular disease of use aspirin for treatment.
9, application as claimed in claim 8 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 200410019846 CN1714827A (en) | 2004-06-30 | 2004-06-30 | Use of medicine in preparing medicine for treating anti-aspirin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410019846 CN1714827A (en) | 2004-06-30 | 2004-06-30 | Use of medicine in preparing medicine for treating anti-aspirin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1714827A true CN1714827A (en) | 2006-01-04 |
Family
ID=35821188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410019846 Pending CN1714827A (en) | 2004-06-30 | 2004-06-30 | Use of medicine in preparing medicine for treating anti-aspirin |
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| Country | Link |
|---|---|
| CN (1) | CN1714827A (en) |
-
2004
- 2004-06-30 CN CN 200410019846 patent/CN1714827A/en active Pending
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