CN101985041A - Clopidogrel- and stanin compounds-containing medicinal composition - Google Patents
Clopidogrel- and stanin compounds-containing medicinal composition Download PDFInfo
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- CN101985041A CN101985041A CN2010105366317A CN201010536631A CN101985041A CN 101985041 A CN101985041 A CN 101985041A CN 2010105366317 A CN2010105366317 A CN 2010105366317A CN 201010536631 A CN201010536631 A CN 201010536631A CN 101985041 A CN101985041 A CN 101985041A
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- clopidogrel
- statin compound
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Abstract
The invention relates to a clopidogrel- and stanin compounds-containing medicinal composition. The clopidogrel and stanin are taken as medicinal active ingredients, some specific types of auxiliary materials in a ratio are added, and oral preparations are prepared and developed according to the technical means in the invention. The composition is used for treating or preventing cardio-cerebrovascular diseases and belongs to the technical field of medicaments.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains clopidogrel and statin compound, belong to medical technical field.
Background technology
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.But the clopidogrel antiplatelet effects can not make all patients be benefited, and there is clopidogrel opposing phenomenon in part patient to the cardiovascular protection effect of clopidogrel, and the patient who promptly uses clopidogrel still the thrombus of heart blood vessel incident can take place.
Statin compound is by the HMG-CoA reductase in the inhibition liver, thereby the biosynthesis of inhibition cholesterol plays the effect that reduces CHO, TG, LP (a), LDL-C, the effect of the HDL-C that raises in addition simultaneously.Statins can not only be regulated total plasma cholesterol and low density lipoprotein, LDL (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol levels, simultaneously can also improve endothelial function, improve and prevent or reverse atherosclerotic plaque, stabilize plaque, regulate inner skin cell function, can obviously reduce plasma C-reactive protein, reduce the inflammatory cell in the atheromatous plaque, reduce the quantity of macrophage, reaction diminishes inflammation.
Thrombotic disease very clinically more sees that thrombosis is that complex factors are caused, and wherein blood vessel wall, platelet, blood flow rate, 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, flow regime changes, may be to slow down or producing the whirlpool shape changes, and sticking collection of platelet and blood flow state change all can promote blood to solidify the formation thrombosis, 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 to present the endarterium lipidosis in large artery trunks and medium-sized artery, form the rotten sample focus of yellow medicated porridge, 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.
Summary of the invention
The present invention relates to a kind of pharmaceutical composition that contains clopidogrel and statin compound, it is to be active component with a kind of statin compound and clopidogrel, is combined to form with acceptable accessories.Wherein clopidogrel comprises its pharmaceutical salts, optical isomer and hydrate, and pharmaceutical salts comprises hydrochlorate, sulfate, disulfate, benzene sulfonate etc.Described statin compound comprises pravastatin, fluvastatin, atorvastatin, Rosuvastatin, Pitavastatin, simvastatin, lovastatin and their pharmaceutical salts thereof etc., and wherein pharmaceutical salts comprises sodium salt, calcium salt, magnesium salt etc.
In the described compositions, the unit formulation input amount of clopidogrel is 5mg～150mg.Be preferably 25-75mg.The unit formulation content of statin compound is 1.25mg～120mg.Be preferably 5mg～40mg.This Pharmaceutical composition can be made into oral formulations: comprise granule, tablet, capsule, soft capsule, chewable tablet, oral cavity disintegration tablet, buccal tablet, drop pill etc.
The present invention also comprises described compositions, treats and/or prevents purposes in the cardiovascular and cerebrovascular vessel incident medicine in preparation.Clopidogrel and statins have nothing in common with each other at intravital mechanism of action of people and site of action, so the two use of joining together can be brought into play synergism, reduce clopidogrel opposing phenomenon, significant minimizing atherosclerosis and the cardiovascular and cerebrovascular vessel thrombosis incident improved.Comprise myocardial infarction, asystole, peripheral blood vessel (comprising symptomatic neck arteries disease), congestive heart failure, ischemic heart disease, angina pectoris (comprising unstable angina pectoris), sudden cardiac death and cerebrovascular events, for example cerebral infarction, cerebral thrombosis, cerebral ischemia and transient ischemic attack etc.
The specific embodiment
Embodiment 1 tablet
Bisulfate clopidogrel is in clopidogrel
Preparation technology:
1, BHA and citric acid are dissolved in an amount of 30% the ethanol
2, vitamin C and PVP are dissolved in an amount of water
3, with lactose, his spit of fland crude drug, cross-linking sodium carboxymethyl cellulose and 10 gram microcrystalline Cellulose mix homogeneously
4, spray into the solution of BHA, add ascorbic solution and granulate, and carry out drying in 60 degree; Granulate, standby
5, get clopidogrel, microcrystalline Cellulose 50 grams, mannitol, low-substituted hydroxypropyl cellulose mix homogeneously, add entry system soft material, granulate, and dry, granulate, standby
6, mix two parts granule, add castor oil hydrogenated, carry out tabletting
7, this tablet is carried out coating, weightening finish 3%-5% gets final product
Embodiment 2: granule
Hybrid particles among the embodiment 1 is filled in the suitable capsule, gets final product.
Embodiment 3: tablet
The benzenesulfonic acid clopidogrel is in clopidogrel
Preparation technology:
1, BHA and citric acid are dissolved in an amount of 30% the ethanol
2, vitamin C and PVP are dissolved in an amount of water
3, with lactose, his spit of fland crude drug, cross-linking sodium carboxymethyl cellulose and 10 gram microcrystalline Cellulose mix homogeneously
4, spray into the solution of BHA, add ascorbic solution and granulate, and carry out drying in 60 degree; Granulate, standby
5, get clopidogrel, microcrystalline Cellulose 50 grams, mannitol, low-substituted hydroxypropyl cellulose mix homogeneously, add entry system soft material, granulate, and dry, granulate, standby
6, mix two parts granule, add castor oil hydrogenated, carry out tabletting
7, this tablet is carried out coating, weightening finish 3%-5% gets final product
Embodiment 4: chewable tablet
The hydrochloric acid clopidogrel is in clopidogrel
Preparation technology:
1, BHA and citric acid are dissolved in an amount of 30% the ethanol
2, vitamin C and PVP are dissolved in an amount of water
3, with lactose, his spit of fland crude drug, cross-linking sodium carboxymethyl cellulose and 10 gram microcrystalline Cellulose mix homogeneously
4, spray into the solution of BHA, add ascorbic solution and granulate, and carry out drying in 60 degree; Granulate, standby
5, get clopidogrel, microcrystalline Cellulose 50 grams, mannitol, sucralose, low-substituted hydroxypropyl cellulose mix homogeneously, add entry system soft material, granulate, and dry, granulate, standby
6, mix two parts granule, add castor oil hydrogenated, carry out tabletting
7, this tablet is carried out coating, weightening finish 3%-5% gets final product
Embodiment 5: antiplatelet aggregation influence experiment:
Assessment clopidogrel and statins combination are 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 bisulfate clopidogrel group, Atorvastatin calcium group, bisulfate clopidogrel+Atorvastatin calcium group, blank 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) use sampler, carefully draw upper strata liquid, promptly are rich in platelet blood plasma (PRP), and room temperature is transferred the usefulness of purchasing.The collagen (Collagen), the adenosine diphosphate (ADP) (ADP) that in different cuvettes, add 11ul with micro-feed liquor device, by external platelet 5min aggregation rate after the medication of turbidimetry usefulness TYXN-91 intelligence blood agglutometer mensuration rat, 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
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
The result shows: with have respectively two kinds of folk prescription medicines of same concentrations and compare, the combination of bisulfate clopidogrel and Atorvastatin calcium has been played significantly reduced effect to inductive hematoblastic coagulation, use bisulfate clopidogrel obvious separately, but it is remarkable to be not so good as the compound recipe effect to antiplatelet agglutination.And use Atorvastatin calcium not produce reduction effect separately to platelet aggregation.Therefore prove that bisulfate clopidogrel and Atorvastatin calcium have synergism to antiplatelet aggregation.
Claims (10)
1. contain the pharmaceutical composition of clopidogrel and statin compound, it is characterized in that, it is to be active component with a kind of statin compound and clopidogrel, is combined to form with acceptable accessories.
2. the described compositions of claim 1 is characterized in that, clopidogrel comprises its pharmaceutical salts, optical isomer and hydrate.
3. the described compositions of claim 2 is characterized in that, the clopidogrel pharmaceutical salts comprises hydrochlorate, sulfate, disulfate, benzene sulfonate etc.
4. the described compositions of claim 1 is characterized in that, statin compound comprises pravastatin, fluvastatin, atorvastatin, Rosuvastatin, Pitavastatin, simvastatin, lovastatin and their pharmaceutical salts thereof etc.
5. the described compositions of claim 4 is characterized in that, the pharmaceutical salts of statin compound comprises sodium salt, calcium salt, magnesium salt etc.
6. the described compositions of claim 1 is characterized in that, the unit formulation input amount of described clopidogrel is 5mg～150mg, is preferably 25-75mg.
7. the described Pharmaceutical composition of claim 1 is characterized in that, the unit formulation content of described statin compound is 1.25mg～120mg, is preferably 5mg～40mg.
8. the described Pharmaceutical composition of claim 1 is characterized in that, can be made into oral formulations.
9. the described Pharmaceutical composition of claim 8 is characterized in that, described oral formulations comprises granule, tablet, capsule, soft capsule, chewable tablet, oral cavity disintegration tablet, buccal tablet, drop pill etc.
10. the described compositions of claim 1, the purposes in preparation treatment and prevention cardiovascular and cerebrovascular vessel incident medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105366317A CN101985041A (en) | 2010-11-08 | 2010-11-08 | Clopidogrel- and stanin compounds-containing medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105366317A CN101985041A (en) | 2010-11-08 | 2010-11-08 | Clopidogrel- and stanin compounds-containing medicinal composition |
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| Publication Number | Publication Date |
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| CN101985041A true CN101985041A (en) | 2011-03-16 |
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| CN2010105366317A Pending CN101985041A (en) | 2010-11-08 | 2010-11-08 | Clopidogrel- and stanin compounds-containing medicinal composition |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690955A (en) * | 2013-12-27 | 2014-04-02 | 福州乾正药业有限公司 | Ticagrelor-containing drug composition as well as preparation method and application thereof |
| CN106955355A (en) * | 2016-01-08 | 2017-07-18 | 北京百奥药业有限责任公司 | Pharmaceutical composition, preparation and its application of statins and Lumbrokinase |
| WO2018135932A3 (en) * | 2017-01-23 | 2018-09-27 | 동화약품주식회사 | Complex formulation comprising hmg-coa reductase inhibitor and clopidogrel |
-
2010
- 2010-11-08 CN CN2010105366317A patent/CN101985041A/en active Pending
Non-Patent Citations (6)
| Title |
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| 叶颖: "他汀类药物和氯吡格雷的相互作用", 《中国药房》 * |
| 李红娟等: "氯吡格雷联合瑞舒伐他汀治疗不稳定型心绞痛的临床研究", 《吉林医学》 * |
| 杨燃等: "氯吡格雷联合辛伐他汀对颈动脉粥样硬化斑块的影响", 《医药论坛杂志》 * |
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| 赵慧艳等: "阿托伐他汀联合氯吡格雷治疗UAP疗效及对IL-6和hs-CRP影响", 《中国现代医生》 * |
| 辛藏玲等: "氯吡格雷联合普伐他汀治疗不稳定型心绞痛疗效观察", 《中国医疗前沿》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690955A (en) * | 2013-12-27 | 2014-04-02 | 福州乾正药业有限公司 | Ticagrelor-containing drug composition as well as preparation method and application thereof |
| CN103690955B (en) * | 2013-12-27 | 2016-04-20 | 福州乾正药业有限公司 | Pharmaceutical composition containing ticagrelor and preparation method thereof and medicinal application |
| CN106955355A (en) * | 2016-01-08 | 2017-07-18 | 北京百奥药业有限责任公司 | Pharmaceutical composition, preparation and its application of statins and Lumbrokinase |
| WO2018135932A3 (en) * | 2017-01-23 | 2018-09-27 | 동화약품주식회사 | Complex formulation comprising hmg-coa reductase inhibitor and clopidogrel |
| CN110198705A (en) * | 2017-01-23 | 2019-09-03 | 同和药品株式会社 | Compound formulation comprising HMG-COA reductase inhibitor and clopidogrel |
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Application publication date: 20110316 |