CN102389436A - Medicinal composition for resisting platelet aggregation - Google Patents
Medicinal composition for resisting platelet aggregation Download PDFInfo
- Publication number
- CN102389436A CN102389436A CN2011102667942A CN201110266794A CN102389436A CN 102389436 A CN102389436 A CN 102389436A CN 2011102667942 A CN2011102667942 A CN 2011102667942A CN 201110266794 A CN201110266794 A CN 201110266794A CN 102389436 A CN102389436 A CN 102389436A
- Authority
- CN
- China
- Prior art keywords
- clopidogrel
- aspirin
- pharmaceutical composition
- salt
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a medicinal composition for resisting platelet aggregation. The medicinal composition is a solid preparation by using aspirin pharmaceutical salt and clopidogrel pharmaceutical salt as active components. The invention aims at making up the defects in the prior art, and supplies a novel preparation which has quick disintegration, fast absorption and convenient administration, and can improve bioavailability and blood concentration of the medicament, shorten the peak reaching time and improve platelet aggregation resistance to broad patients and medical staff. The oral solid preparation is prepared by using aspirin pharmaceutical salt and clopidogrel pharmaceutical salt as raw materials, and adding auxiliary materials with certain specific varieties and proportions according to a pharmaceutical conventional technology.
Description
Technical field
These article are a kind of pharmaceutical composition of antiplatelet aggregation, belong to medical technical field.
Background technology
Thrombotic disease very clinically more sees that thrombosis is that complex factors are caused, and wherein blood vessel wall, platelet, VPV, blood viscosity and blood coagulation activity etc. all play an important role.Platelet count is higher; It is the factor that can cause thrombosis that blood fat increases. the thrombocytosis meeting makes the chance of the sticking collection of platelet big; Blood fat increases can make blood viscosity increase, and flow regime changes, and possibly be to slow down or produces the change of whirlpool shape; Change all can promote blood to solidify the formation thrombosis and the sticking collection of platelet is with blood flow state, so antiplatelet aggregation, blood fat reducing content are extremely important in antithrombotic therapy.
Atherosclerosis is the commonly encountered diseases and the frequently-occurring disease of old and middle age; It is owing in large artery trunks and medium-sized artery, present the endarterium lipidosis; Form the rotten appearance of yellow medicated porridge focus, fibroplasia and hardening appear in arterial wall, are the main causes that forms heart and cerebral ischemia disease.In many countries and regions, atherosclerosis and complication thereof occupy the first place of the cause of death.About atherosclerotic mechanism, theories such as lipid infiltration, proliferation of smooth muscle, thrombosis, platelet aggregation and endarterium damage are arranged.Therefore blood fat reducing content promotes fibrinolytic, anticoagulant and anticoagulant, is antiatherogenic key.
Aspirin is the antiplatelet drug that is applied to the thromboembolism preventing treatment the earliest, has been established as treatment acute myocardial infarction (AMI), the classical medication of UA and myocardial infarction (MI) second phase prevention.The aspirin mechanism of action is to make and loses activity after the 529th the serine acetylation of Cycloxygenase active site in the platelet arachidonic acid metabolic pathway and suppress TXA2. and generate, thereby stops platelet aggregation and release reaction.
Clopidogrel is a kind of novel thiophene pyridine derivatives; Its active metabolite alternative irreversibly combines with platelet surface adenosine diphosphate (ADP) (ADP) receptor P2Y12; Reduce the ADP binding site; Blocking-up ADP is to the inhibitory action of adenosine cyclase; Promote the proteic phosphorylation of vasodilator material phosphoric acid that cAMP relies on, the activation of the glycoprotein GPIIb/IIIa complex of the ADP mediation of inhibition Fibrinogen and platelet glycoprotein GPIIb/IIIa receptors bind and secondary, and then suppress hematoblastic gathering.In Antiplatelet therapy, clopidogrel has been represented an important progress, multinomial experiment confirm clopidogrel to patients such as all coronary heart disease from acute stage to secular protective effect.
Summary of the invention
The present invention relates to a kind of pharmaceutical composition of antiplatelet aggregation, it is characterized in that, is to be that active component and pharmaceutic adjuvant combine with aspirin pharmaceutical salts and clopidogrel pharmaceutical salts.
Compound preparation provided by the invention contains aspirin pharmaceutical salts, clopidogrel pharmaceutical salts and is fit to process the excipient substance of solid preparation, and wherein the unit formulation input amount of aspirin pharmaceutical salts is 20-600mg, preferred 80-300mg.The unit formulation input amount of clopidogrel pharmaceutical salts is 20-300mg, preferred 75-150mg.
Said adjuvant is selected from disintegrating agent, filler, binding agent, lubricant; Surfactant, sweeting agent, wherein the percentage by weight of filler is 20-90%; The percentage by weight of disintegrating agent is 5-30%; The percentage by weight of binding agent is that the percentage by weight of 1-30%, lubricant is 0.1-5%, and the percentage by weight of surfactant is 0.1-5%, and the percentage by weight of lubricant is 0.1-5%.
Disintegrating agent wherein includes but not limited to one or more in carboxymethyl starch sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, cross-linked carboxymethyl cellulose calcium, the microcrystalline Cellulose; Surfactant comprises but is not limited to sodium lauryl sulphate, cetyl sulfo-sodium succinate, sodium dioctyl sulfosuccinate, tween 80, docusate sodium; Filler includes but not limited to one or more in lactose, sucrose, sorbitol, mannitol, xylitol, erythritol, pregelatinized Starch, starch, the microcrystalline Cellulose; Binding agent includes but not limited to a kind of in ethanol, water, ethanol-water solution, syrup, starch slurry, carboxymethylcellulose sodium solution, povidone solution, hydroxypropyl cellulose solution, the sodium alginate soln or wherein several kinds; Sweeting agent comprises but is not limited to aspartame, acesulfame potassium, sucralose, saccharin sodium, one or more in the sodium cyclamate; Lubricant wherein includes but not limited to one or more among micropowder silica gel, magnesium stearate, calcium stearate, stearic acid, Pulvis Talci, silicon dioxide, sodium lauryl sulphate, PEG4000, the PEG6000.
Wherein correctives includes but not limited to one or more the mixture in flavoring orange essence, Herba Menthae essence, grape essence, cherry essence, flavoring banana essence, flavoring pineapple essence, vanilla, Fructus Citri Limoniae essence, aspartame, saccharin sodium, the steviol glycosides; Consumption is 0.5-5%.
The most preferred prescription composition of the present invention is listed among the embodiment.
The specific embodiment
Following case study on implementation is used to explain the present invention, but is not limited thereto.
Embodiment 1 tablet
| The supplementary material title | Consumption |
| Aspirin (lysinate) | 80g |
| Clopidogrel (disulfate) | 75g |
| Microcrystalline Cellulose | 86g |
| Lactose | 26.6g |
| Sodium carboxymethyl cellulose | 9.0g |
| Hydroxypropyl cellulose | 6.0g |
| Magnesium stearate | 2.4g |
| Purified water | In right amount |
Technology: get above-mentioned each crude drug, pulverize separately is crossed 80 mesh sieves, and is subsequent use; Each adjuvant is crossed 60 mesh sieves respectively, and is subsequent use; Except that magnesium stearate, get each supplementary material respectively, mix homogeneously adds suitable quantity of water system soft material, and 18 orders are granulated, 60 degree fluid bed dryings, 24 order granulate add magnesium stearate, mix homogeneously, tabletting.
Embodiment 2 capsules
| The supplementary material title | Consumption |
| Aspirin (zinc salt) | 80g |
| Clopidogrel (hydrochlorate) | 75g |
| Microcrystalline Cellulose | 40.4g |
| Sodium carboxymethyl cellulose | 9.2g |
| Hydroxypropyl cellulose | 4.0g |
| Silicon dioxide | 4.6g |
| Magnesium stearate | 1.8g |
| Purified water | In right amount |
Technology: get above-mentioned each crude drug, pulverize separately is crossed 80 mesh sieves, and is subsequent use; Each adjuvant is crossed 60 mesh sieves respectively, and is subsequent use; Except that silicon dioxide, magnesium stearate, get each supplementary material respectively, mix homogeneously adds suitable quantity of water system soft material, and 18 orders are granulated, 60 ℃ of dryings, 24 order granulate add silicon dioxide, magnesium stearate, behind the mix homogeneously, insert in the capsulae vacuus, promptly get.
Embodiment 3: chewable tablet
| The supplementary material title | Consumption |
| Aspirin (arginine salt) | 80g |
| Clopidogrel (benzene sulfonate) | 75g |
| Lactose | 50g |
| Cross-linking sodium carboxymethyl cellulose | 20g |
| PVP?K30 | 2g |
| PEG?6000 | 50g |
| Citric acid | 50g |
| Microcrystalline Cellulose PH-101 | 200g |
| Low-substituted hydroxypropyl cellulose | 20g |
| Sucralose | 1g |
| The powder orange flavor | 12g |
| Mannitol | 50g |
| Castor oil hydrogenated | 5g |
| Coating powder | In right amount |
Preparation technology:
1.PVP be dissolved in an amount of water;
2. with lactose, aspirin crude drug, cross-linking sodium carboxymethyl cellulose and 150 gram microcrystalline Cellulose mix homogeneously;
3. the aqueous solution that adds PVP is granulated, and carries out drying in 60 degree; Granulate, subsequent use;
4. get clopidogrel, microcrystalline Cellulose 50 grams, mannitol, citric acid, low-substituted hydroxypropyl cellulose mix homogeneously, add entry system soft material, granulate, and dry, granulate, subsequent use;
5. with step 3 and step 4 two parts granule mixing, add PEG 6000, sucralose, powder orange flavor, castor oil hydrogenated mix homogeneously, tabletting, coating promptly gets.
Embodiment 4: granule
| The supplementary material title | Consumption |
| Aspirin (amino butanetriol salt) | 100g |
| Clopidogrel (mesylate) | 75g |
| Lactose | 80g |
| Microcrystalline Cellulose | 85g |
| Cross-linking sodium carboxymethyl cellulose | 10g |
| Silicon dioxide | 2g |
| Magnesium stearate | 2g |
Technology: get above-mentioned each crude drug, pulverize separately is crossed 80 mesh sieves, and is subsequent use; Each adjuvant is crossed 60 mesh sieves respectively, and is subsequent use; Except that silicon dioxide, magnesium stearate, get each supplementary material respectively, mix homogeneously adds suitable quantity of water system soft material, and 18 orders are granulated, 60 ℃ of dryings, 24 order granulate add silicon dioxide, magnesium stearate, and behind the mix homogeneously, fill promptly gets.
Embodiment 5: slow releasing tablet
| The supplementary material title | Consumption |
| Aspirin (sodium salt) | 100g |
| Clopidogrel (hydrobromate) | 80g |
| Lactose | 70g |
| Microcrystalline Cellulose | 85g |
| HPMC?K4M | 10g |
| Silicon dioxide | 2g |
| Magnesium stearate | 2g |
Technology: get above-mentioned each crude drug, pulverize separately is crossed 80 mesh sieves, and is subsequent use; Each adjuvant is crossed 60 mesh sieves respectively, and is subsequent use; Except that silicon dioxide, magnesium stearate, get each supplementary material respectively, with equivalent incremental method mix homogeneously, add 90% ethanol system soft material, 18 mesh sieves are granulated, 60 ℃ of oven dry, 24 mesh sieve granulate.Add colloidal silica, magnesium stearate, mix homogeneously, tabletting.
Embodiment 6: dispersible tablet
| The supplementary material title | Consumption |
| Aspirin (calcium salt) | 110g |
| Clopidogrel (benzoate) | 85g |
| Microcrystalline Cellulose | 50g |
| Cross-linking sodium carboxymethyl cellulose | 25g |
| Hyprolose | 20g |
| Aspartame | 5g |
| Silicon dioxide | 2g |
| Magnesium stearate | 2g |
| Orange flavor | 1g |
Technology: earlier raw material pulverizing is crossed 100 mesh sieves, behind crude drug, microcrystalline Cellulose, the abundant mix homogeneously of hyprolose, add an amount of water system soft material; 18 mesh sieves are granulated; 60 ℃ after dry 3-4 hour, 24 mesh sieve granulate add disintegrating agent cross-linking sodium carboxymethyl cellulose, aspartame, silicon dioxide, magnesium stearate outward; Behind the mixing, be pressed into dispersible tablet.
Embodiment 7: antiplatelet aggregation influence experiment:
The assessment aspirin phenacetin caffeine is to hematoblastic agglutination
Get 40 healthy SD rats; In the body weight 180-220g target zone; Be divided into four groups at random, be respectively aspirin (A), clopidogrel (B), clopidogrel+aspirin (C), benzenesulfonic acid clopidogrel+Aspirin-arginine (D), bisulfate clopidogrel+lysine propylhomoserin aspirin (E), hydrochloric acid clopidogrel+aspirin zinc (F), blank (0) group.Each organizes equal gastric infusion 7 days, 2h after the last administration, after anaesthetizing from abdominal aortic blood.
Get behind the blood with 3.8% sodium citrate anticoagulant (9: 1), mixing.Be sub-packed in the test tube, the autobalance centrifuge, 1000 rev/mins centrifugal 5～8 minutes (under 20～25 ℃ of conditions) are used sampler, carefully draw upper strata liquid, promptly are rich in platelet blood plasma (PRP), and the room temperature held is subsequent use.The collagen (Collagen), the adenosine diphosphate (ADP) (ADP) that in different cuvettes, add 11ul with micro-feed liquor device; By turbidimetry with the medications of the intelligent blood agglutometers mensuration of TYXN 1 rat after external platelet 5min PAR, calculate platelet aggregation inhibition rate simultaneously.Assemble suppression ratio %=(control tube is assembled percentage rate-developmental tube and assembled percentage rate)/control tube and assemble percentage rate * 100
The result: compare with folk prescription aspirin, clopidogrel and aspirin phenacetin caffeine clopidogrel medicine, the compound recipe of aspirin salt and clopidogrel salt is more obvious to antiplatelet agglutination.
Table 1 pair collagen and adenosine diphosphate (ADP) are induced the influence (N=10) of rats in vitro agglutinate rate of blood platelet, suppression ratio
Claims (8)
1. the pharmaceutical composition of antiplatelet aggregation is characterized in that, is to be active component with aspirin pharmaceutical salts and clopidogrel pharmaceutical salts, combines with pharmaceutically suitable adjuvant.
2. the described pharmaceutical composition of claim 1 is characterized in that, the aspirin pharmaceutical salts is for comprising: arginine salt, lysinate, amino butanetriol salt, sodium salt, calcium salt, zinc salt, magnesium salt etc.
3. the described pharmaceutical composition of claim 1; It is characterized in that the clopidogrel pharmaceutical salts comprises: hydrochlorate, disulfate, benzene sulfonate, mesylate, hydrobromate, benzoate, oxalates, lactate, fumarate, tartrate, gluconate etc.
4. the described pharmaceutical composition of claim 1 is characterized in that, the unit consumption of described aspirin pharmaceutical salts is: in an Ah Si 20-600mg, be preferably 80～300mg.
5. the described pharmaceutical composition of claim 1 is characterized in that, the unit consumption of described clopidogrel pharmaceutical salts is: in clopidogrel 20-300mg, be preferably 75～150mg.
6. the described pharmaceutical composition of claim 1 is characterized in that: can be made into oral formulations, comprise granule, ordinary tablet, chewable tablet, dispersible tablet, oral cavity disintegration tablet, buccal tablet, capsule, slow releasing tablet etc.
7. the described pharmaceutical composition of claim 1 is treated by platelet aggregation the purposes in the inductive disease medicament in preparation.
8. the described compositions of claim 7, described purposes is treatment and the prevention that can be used for various thrombotic diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102667942A CN102389436A (en) | 2011-09-09 | 2011-09-09 | Medicinal composition for resisting platelet aggregation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102667942A CN102389436A (en) | 2011-09-09 | 2011-09-09 | Medicinal composition for resisting platelet aggregation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102389436A true CN102389436A (en) | 2012-03-28 |
Family
ID=45856901
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102667942A Pending CN102389436A (en) | 2011-09-09 | 2011-09-09 | Medicinal composition for resisting platelet aggregation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102389436A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102976962A (en) * | 2012-11-20 | 2013-03-20 | 万红贵 | L-ornithine-aspirin double salt and its preparation method and use |
| CN104257668A (en) * | 2014-09-19 | 2015-01-07 | 深圳奥萨医药有限公司 | Pharmaceutical composition containing aspirin, clopidogrel and folic acid compound |
| CN104367582A (en) * | 2014-05-20 | 2015-02-25 | 南京海纳医药科技有限公司 | Tablet containing clopidogrel sulfate and aspirin active compositions and preparation method thereof |
| CN104523710A (en) * | 2014-12-30 | 2015-04-22 | 石药集团欧意药业有限公司 | Compound clopidogrel hydrogen sulphate and aspirin double-layer tablet and preparation method thereof |
| CN106166298A (en) * | 2015-05-21 | 2016-11-30 | 张键 | Use citric acid as the correctives of Aspirin chewable tablets and stabilizer |
| WO2017037741A1 (en) * | 2015-09-02 | 2017-03-09 | Sun Pharmaceutical Industries Ltd | Compact solid dosage form of aspirin and clopidogrel |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1211922A (en) * | 1996-02-19 | 1999-03-24 | 萨诺费公司 | Associations of active principles containing clopidogrel and antithrombotic agent |
-
2011
- 2011-09-09 CN CN2011102667942A patent/CN102389436A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1211922A (en) * | 1996-02-19 | 1999-03-24 | 萨诺费公司 | Associations of active principles containing clopidogrel and antithrombotic agent |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102976962A (en) * | 2012-11-20 | 2013-03-20 | 万红贵 | L-ornithine-aspirin double salt and its preparation method and use |
| CN102976962B (en) * | 2012-11-20 | 2015-02-04 | 南京工业大学 | L-ornithine-aspirin double salt and preparation method and application thereof |
| CN104367582A (en) * | 2014-05-20 | 2015-02-25 | 南京海纳医药科技有限公司 | Tablet containing clopidogrel sulfate and aspirin active compositions and preparation method thereof |
| CN104257668A (en) * | 2014-09-19 | 2015-01-07 | 深圳奥萨医药有限公司 | Pharmaceutical composition containing aspirin, clopidogrel and folic acid compound |
| CN104523710A (en) * | 2014-12-30 | 2015-04-22 | 石药集团欧意药业有限公司 | Compound clopidogrel hydrogen sulphate and aspirin double-layer tablet and preparation method thereof |
| CN104523710B (en) * | 2014-12-30 | 2018-05-25 | 石药集团欧意药业有限公司 | A kind of bisulfate clopidogrel aspirin Composite Double synusia and preparation method thereof |
| CN106166298A (en) * | 2015-05-21 | 2016-11-30 | 张键 | Use citric acid as the correctives of Aspirin chewable tablets and stabilizer |
| WO2017037741A1 (en) * | 2015-09-02 | 2017-03-09 | Sun Pharmaceutical Industries Ltd | Compact solid dosage form of aspirin and clopidogrel |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102389436A (en) | Medicinal composition for resisting platelet aggregation | |
| KR102024699B1 (en) | Complex formulation comprising clopidogrel and asprin | |
| KR20160030297A (en) | Traditional chinese medicine composition, and preparation and application thereof | |
| TW201526921A (en) | Ticagrelor solid dispersion and preparation method thereof | |
| JP2018039854A (en) | Pharmaceutical composition of formula (i) compound, dosage form, and novel form, as well as method of use thereof | |
| WO2013189285A1 (en) | Application of piceatannol-3'-o-β-d-glucopyranoside in preparation of medicaments for improving microcirculation block | |
| CN115518066A (en) | Pharmaceutical composition for treating anticoagulation and application | |
| CN100374107C (en) | Preparation of honokiol, magnolol or their admixture and usage in preparing medication for treating cardiovascular and cerebrovascular diseases | |
| CN102228691A (en) | Aspirin and anticoagulant pharmaceutical composition | |
| CN1762341B (en) | Salvianolic acid compound for treating cardiovascular and cerebrovascular disease and liver disease, and application thereof | |
| CN101879169B (en) | Compound preparation for treating relevant vascular diseases and preparation method thereof | |
| CN112999214B (en) | Application of homovanillic acid in preparation of anti-platelet aggregation medicine | |
| CN101985041A (en) | Clopidogrel- and stanin compounds-containing medicinal composition | |
| CN103800336A (en) | Composition with anti-thrombus active medicine | |
| CN103735552B (en) | Pharmaceutical composition of ticagrelor and cilostazol and its preparation method and application | |
| CN102125690A (en) | Application of polyphenol components in preparation of medicaments for treating aspirin resistance | |
| JP7189873B2 (en) | Powdery solid compositions, methods for their production, formulations and uses thereof | |
| CN102552353A (en) | Chinese medicinal composition containing Chinese angelica and preparation method thereof | |
| CN101984969A (en) | Drug composition containing clopidogrel and fibrate compounds | |
| CN101984971A (en) | Drug composition containing clopidogrel and nicotinic acid compounds | |
| CN102755319B (en) | Pharmaceutical composition containing prasugrel and carvedilol, and purpose thereof | |
| CN104721220B (en) | A kind of pharmaceutical composition and its application, preparation | |
| CN101637464B (en) | Drug composite containing calcium 2,5-dihydroxysulfonate and ADP receptor antagonist | |
| JP6910103B2 (en) | Oral preparation | |
| WO2014015507A1 (en) | Application of shengui capsule in preparing antithrombotic drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120328 |