CN100381133C - Application of pharmaceutical composition in the process for preparing medicine to treat aspirin resisting disease - Google Patents
Application of pharmaceutical composition in the process for preparing medicine to treat aspirin resisting disease Download PDFInfo
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- 239000003814 drug Substances 0.000 title claims abstract description 37
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims description 58
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims description 54
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 30
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 2
- 201000010099 disease Diseases 0.000 title 1
- 208000025870 aspirin resistance Diseases 0.000 claims abstract description 31
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims abstract description 13
- 235000003143 Panax notoginseng Nutrition 0.000 claims abstract description 13
- 241000180649 Panax notoginseng Species 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 238000011282 treatment Methods 0.000 claims description 16
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 14
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 13
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 10
- 206010002383 Angina Pectoris Diseases 0.000 claims description 8
- 208000029078 coronary artery disease Diseases 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 4
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- 229940116229 borneol Drugs 0.000 abstract 1
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- 238000013329 compounding Methods 0.000 abstract 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 abstract 1
- 235000005412 red sage Nutrition 0.000 abstract 1
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- XNRNNGPBEPRNAR-JQBLCGNGSA-N thromboxane B2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1OC(O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O XNRNNGPBEPRNAR-JQBLCGNGSA-N 0.000 description 4
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- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to the application of a medicine composition in the process for preparing medicine to treat aspirin resistance. The medicine has the components of the following compounding ratio by weight: 50 to 60 portions of red sage root, 16 to 20 portions of radix notoginseng and 0.1 to 3 portions of borneol, and the medicine can be made into any preparation which can be accepted on pharmacy.
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to the application of a kind of pharmaceutical composition in preparation treatment aspirin resistance medicine.
Background technology
Aspirin (Aspirin) is 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
Platelet aggregation 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 plateletfunction:lack if prevention by aspirin in men with coronary artery disease.J Lab ClinMed, 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 then platelet activation that catecholamine causes and the acute coronary syndrome, Norepinephrine-induced human platelet activation in vivo is onlypartly counteracted 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.
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).
[Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction such as John W., stroke, or cardiovascular death in patients at high risk for cardiovascular events.] by measuring the 11-dehydrogenation TXB in patient's urine
2Content has been studied the aspirin resistance phenomenon.The result shows, in the patient of aspirin for treatment, and 11-dehydrogenation TXB in the urine
2Content can be predicted the risk of myocardial infarction and cardiovascular disease death.These discoveries have increased such probability, and that is exactly 11-dehydrogenation TXB in the urine
2The patient that content raises, its easy relatively more aspirin resistance that causes, they may be benefited from other the medicine of antiplatelet aggregation so, thereby suppress more effectively that thromboxane produces and active.
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.
Through secular clinical practice, chosen the pharmaceutical composition of forming by Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum etc. by the people, make tablet, have blood circulation promoting and blood stasis dispelling, the merit of regulating QI to relieve pain is used for clinical treatment coronary heart disease, uncomfortable in chest, anginal treatment clinically.
In recent years, the report about this pharmaceutical composition is a lot.The new clinical research of relevant this pharmaceutical composition also has a lot of reports, except can being used for coronary heart disease, angina pectoris, can also be used for the treatment of bronchial asthma, trigeminal neuralgia and dysmenorrhea etc. clinically, and has been subjected to satisfied curative effect.
But there is this medicine composite for curing aspirin resistance effect not appear in the newspapers as yet.
Summary of the invention
The present invention is the new purposes invention of finishing on the basis of aforementioned pharmaceutical compositions, and the composition of prescription is as follows by weight ratio:
50～60 parts of Radix Salviae Miltiorrhizaes, 16～20 parts of Radix Notoginseng, 0.1～3 part of Borneolum Syntheticum.
Wherein, preferred proportion is 58 parts of Radix Salviae Miltiorrhizaes, 18 parts of Radix Notoginseng, 1 part of Borneolum Syntheticum.
This preparation of drug combination method is as follows:
Extract Radix Salviae Miltiorrhizae in the following manner 3 times: alcohol heating reflux 1.5 hours, filter, reclaim ethanol, concentrated filtrate becomes concentrated solution, and relative density is 1.30 (55-60 ℃); To remain medical material and use 50% alcohol heating reflux 1.5 hours, filter; Continue to add water reflux medical material 2 hours, filter.The extracting solution that merges second and third time reclaims ethanol, and being concentrated into relative density is 1.40 (55-60 ℃), merges with the concentrated solution that extracts for the first time, makes the extractum of relative density 1.35-1.39 (55-60 ℃).
Radix Notoginseng is pulverized, and above-mentioned spissated Radix Salviae Miltiorrhizae extractum mixes, and is dried to granule.
Grind Borneolum Syntheticum and become fine powder, mix, make plain sheet or coated tablet with above-mentioned granule.
Above-mentioned pharmaceutical composition can be made any one dosage form on the pharmaceutics by methods known in the art, and wherein, preferred dosage form is capsule or tablet or granule or oral liquid etc.
Using the low-dosage aspirin treatment and preventing coronary heart disease, angina pectoris is one of modern medicine means commonly used, shows good clinical effectiveness.But Epidemiological study shows some cardiovascular and cerebrovascular disease patient life-time service aspirin, with the generation of prevention cardiovascular and cerebrovascular disease, not only does not bring about the desired effect, and untoward reaction increases on the contrary, and this phenomenon is called as " aspirin resistance " clinically.
Because aspirin resistance often betides among the cardiovascular and cerebrovascular disease patient, so aspirin resistance of the present invention is an aspirin repellency cardiovascular and cerebrovascular disease; Promptly use aspirin for treatment invalid cardiovascular and cerebrovascular disease, particularly aspirin for treatment invalid coronary heart disease, angina pectoris.The said pharmaceutical composition of the present invention has the effect of anti-aspirin resistance.
Tried patient's urina sanguinis stage casing 11-dehydrogenation TXB by measurement
2Content has been studied the effect of medicine composite for curing aspirin resistance of the present invention.Wherein, the therapeutical effect of aspirin resistance is meant that the aspirin resistance patient uses this pharmaceutical composition separately, or the associating aspirin is when using together, 11-dehydrogenation TXB in its urine
2Content is with low.Experiment shows, its 11-dehydrogenation TXB
2Content descends low more, and the effect of its treatment aspirin resistance is just good more.In this this experiment, the former blood circulation promoting and blood stasis dispelling that belongs to, the pharmaceutical composition of the present invention of regulating QI to relieve pain class medicine has the effect of anti-" aspirin resistance ".
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 ".
11-dehydrogenation TXB in patient's urine
2Content is the index that can represent the mankind's " aspirin resistance " of generally acknowledging at present.This test is adopted and is measured 11-dehydrogenation TXB in patient's urina sanguinis
2Content, illustrate take medicine before and after patients " aspirin resistance " the improvement situation.
Physical data
This organizes 177 routine patients all from the General Logistics Department first cadre's sanitarium, the eight cadre's sanitarium retired personnels of branch.Male 140 people wherein, women 37 people.70 years old～87 years old age, 77.1 years old mean age.Select 170 people at random and carry out the specimen detection, and data tolerance interval 150 people (IC20～IC80).Charge among the statistician clothes aspirin person 50 people; Take this pharmaceutical composition 50 people; Sharer 50 people (all patient took medicine more than half a year at least continuously to the day of sampling), wherein 91 people are associated with history of hypertension, and 25 people have hyperlipidemia, and 32 people have diabetes, and 139 people have coronary heart disease, and 57 people have cerebrovascular disease.
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-8 ℃ 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
Average between group is carried out the t-check, resistant's frequency between group is carried out x
2Check.
Table 1. is respectively organized patient's urine value 11-dehydrogenation TXB
2(ng/mmol)
Conclusion: obvious significant difference is arranged, t=2.50 p＜0.05 between the TXB2 excretion in the urine between this pharmaceutical composition and aspirin combination group (pharmaceutical composition+Ah) and aspirin use group separately group; Obvious significant difference is also arranged, t=1.99 p＜0.05 between the TXB2 excretion in the urine between pharmaceutical composition group and aspirin group group; No obvious significant difference between the TXB2 excretion during pharmaceutical composition group and pharmaceutical composition share and urinate between aspirin (pharmaceutical composition+Ah) group group, t=0.62 p＞0.05.
This experimental result proves, should want compositions 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 pharmaceutical composition has anti-aspirin resistance effect, the cardiovascular patient invalid to aspirin, this pharmaceutical composition still has the effect that improves life index.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
A. get Radix Salviae Miltiorrhizae 450g, Radix Notoginseng 141g, Borneolum Syntheticum 8g;
B. extract Radix Salviae Miltiorrhizae in the following manner 3 times: alcohol heating reflux 1.5 hours, filter, reclaim ethanol, concentrated filtrate becomes concentrated solution, and relative density is 1.30 (55-60 ℃); To remain medical material and use 50% alcohol heating reflux 1.5 hours, filter;
Continue to add water reflux medical material 2 hours, filter.The extracting solution that merges second and third time reclaims ethanol, and being concentrated into relative density is 1.40 (55-60 ℃), merges with the concentrated solution that extracts for the first time, makes the extractum of relative density 1.35-1.39 (55-60 ℃).
C. Radix Notoginseng is pulverized, above-mentioned spissated Radix Salviae Miltiorrhizae extractum mixes, and is dried to granule.
D. grind Borneolum Syntheticum and become fine powder, mix, make 1000 with above-mentioned granule.
Embodiment 2
A. get Radix Salviae Miltiorrhizae 450g, Radix Notoginseng 141g, Borneolum Syntheticum 8g;
B. extract Radix Salviae Miltiorrhizae in the following manner 3 times: alcohol heating reflux 1.5 hours, filter, reclaim ethanol, concentrated filtrate becomes concentrated solution, and relative density is 1.30 (55-60 ℃); To remain medical material and use 50% alcohol heating reflux 1.5 hours, filter;
Continue to add water reflux medical material 2 hours, filter.The extracting solution that merges second and third time reclaims ethanol, and being concentrated into relative density is 1.40 (55-60 ℃), merges with the concentrated solution that extracts for the first time, makes the extractum of relative density 1.35-1.39 (55-60 ℃).
C. Radix Notoginseng is pulverized, above-mentioned spissated Radix Salviae Miltiorrhizae extractum mixes, and is dried to granule.
D. grind Borneolum Syntheticum and become fine powder, mix, make 1000, sugar coating with above-mentioned granule.
Embodiment 3
A. get Radix Salviae Miltiorrhizae 480g, Radix Notoginseng 130g, Borneolum Syntheticum 7g;
B. extract Radix Salviae Miltiorrhizae in the following manner 3 times: alcohol heating reflux 1.5 hours, filter, reclaim ethanol, concentrated filtrate becomes concentrated solution, and relative density is 1.30 (55-60 ℃); To remain medical material and use 50% alcohol heating reflux 1.5 hours, filter;
Continue to add water reflux medical material 2 hours, filter.The extracting solution that merges second and third time reclaims ethanol, and being concentrated into relative density is 1.40 (55-60 ℃), merges with the concentrated solution that extracts for the first time, makes the extractum of relative density 1.35-1.39 (55-60 ℃).
C. Radix Notoginseng is pulverized, above-mentioned spissated Radix Salviae Miltiorrhizae extractum mixes, and is dried to granule.
D. grind Borneolum Syntheticum and become fine powder, mix, make 1000, sugar coating with above-mentioned granule.
Claims (7)
1. the application of pharmaceutical composition in the medicine of the anti-aspirin resistance of preparation, wherein said pharmaceutical composition is made up of the crude drug of following weight ratio:
50～60 parts of Radix Salviae Miltiorrhizaes, 16～20 parts of Radix Notoginseng, 0.1～3 part of Borneolum Syntheticum.
2. the application of a kind of pharmaceutical composition according to claim 1 in the medicine of the anti-aspirin resistance of preparation is characterized in that the weight proportion of described each flavour of a drug of pharmaceutical composition is as follows:
58 parts of Radix Salviae Miltiorrhizaes, 18 parts of Radix Notoginseng, 1 part of Borneolum Syntheticum.
3. the application of a kind of pharmaceutical composition according to claim 1 in the medicine of the anti-aspirin resistance of preparation is characterized in that described pharmaceutical composition can make any one dosage form on the pharmaceutics.
4. the application of a kind of pharmaceutical composition according to claim 3 in the medicine of the anti-aspirin resistance of preparation is characterized in that described dosage form is a kind of of capsule, granule or oral liquid.
5. according to claim 1,2, the application of 3 or 4 described a kind of pharmaceutical compositions in the preparation resistant medication anti aspirin, it is characterized in that the application of this pharmaceutical composition in the medicine of preparation treatment aspirin repellency cardiovascular and cerebrovascular disease.
6. purposes according to claim 5 is characterized in that described aspirin repellency cardiovascular and cerebrovascular disease is meant the invalid cardiovascular and cerebrovascular disease of use aspirin for treatment.
7. purposes according to claim 5 is characterized in that described aspirin repellency cardiovascular and cerebrovascular disease is meant invalid coronary heart disease or the angina pectoris of use aspirin for treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101220388A CN100381133C (en) | 2003-12-31 | 2003-12-31 | Application of pharmaceutical composition in the process for preparing medicine to treat aspirin resisting disease |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101220388A CN100381133C (en) | 2003-12-31 | 2003-12-31 | Application of pharmaceutical composition in the process for preparing medicine to treat aspirin resisting disease |
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|---|---|
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| CN100381133C true CN100381133C (en) | 2008-04-16 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1421239A (en) * | 2002-12-23 | 2003-06-04 | 北京采瑞医药有限公司 | Compound red sage prepn for treating cardiac and cerebral vascular diseases and its prepn process |
-
2003
- 2003-12-31 CN CNB2003101220388A patent/CN100381133C/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1421239A (en) * | 2002-12-23 | 2003-06-04 | 北京采瑞医药有限公司 | Compound red sage prepn for treating cardiac and cerebral vascular diseases and its prepn process |
Non-Patent Citations (1)
| Title |
|---|
| 冠心病患者的阿司匹林抵抗现象. 涂昭辉.广东医学，第24卷第2期. 2003 * |
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