CN103720700A - Medical composition containing aspirin and vicagrel - Google Patents
Medical composition containing aspirin and vicagrel Download PDFInfo
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- CN103720700A CN103720700A CN201310435324.3A CN201310435324A CN103720700A CN 103720700 A CN103720700 A CN 103720700A CN 201310435324 A CN201310435324 A CN 201310435324A CN 103720700 A CN103720700 A CN 103720700A
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- acid
- aspirin
- card gray
- acceptable salt
- pharmaceutically acceptable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention relates to the field of pharmacy, in particular to medical composition containing vicagrel or pharmaceutically acceptable salt and aspirin which are taken as effective components, as well as an application of the medical composition containing vicagrel or pharmaceutically acceptable salt and aspirin which are taken as effective components in preparation of a medicine for preventing or curing diseases caused by thrombus. Besides, the invention further provides a method for utilizing the medical composition containing vicagrel or harmaceutically acceptable salt and aspirin which are taken as effective components for preventing or curing the diseases caused by thrombus, and particularly provides a therapeutic method.
Description
Technical field
The present invention relates to pharmaceutical field, be specifically related to contain dimension card Gray or its pharmaceutically acceptable salt and the aspirin Pharmaceutical composition as effective ingredient, and the purposes in the medicine that contains the disease that dimension card Gray or its pharmaceutically acceptable salt and aspirin cause by thrombosis in preparation prevention or treatment as the Pharmaceutical composition of effective ingredient.In addition, the present invention also provide using contain dimension card Gray or its pharmaceutically acceptable salt and aspirin as the Pharmaceutical composition of effective ingredient for preventing or treat the method for the disease being caused by thrombosis, especially Therapeutic Method.
Present patent application requires the priority of Chinese patent application (application number 201210382331.7, the applying date: on October 10th, 2012, invention and created name: the Pharmaceutical composition that contains aspirin and Wei Ka Gray).
Background technology
The anti-platelet aggregation medicinal that dimension card Gray researches and develops recently, this compound is first disclosed as in Chinese patent application 201010104091.5 and 201010624329.7, chemistry is by name: (S)-2-(2-acetoxyl group-6,7-dihydro-thiophene is [3,2-c] pyridine-5 (4H)-yl also)-2-(2-chlorphenyl)-methyl acetate.The dimension card Gray in vivo metabolism step of the first step is to generate clopidogrel thiolactone through intestinal esterase hydrolyzed, through peroxidating open loop, generate clopidogrel active metabolite again, thereby avoided the metabolic pathway of liver CYP2C19, thereby be considered to fundamentally to overcome " clopidogrel Resistant " (J Med Chem, 2012,55,3342).
On the other hand, known aspirin has weak platelet aggregation inhibitory action.But the pharmaceutical composition that dimension card Gray and aspirin are combined is not known.
Summary of the invention
The object of the present invention is to provide a kind of Pharmaceutical composition and Therapeutic Method of more efficiently treatment thrombotic disease.The inventor is through body Nei Yuedai kinetics and pharmacodynamic study, be surprised to find by the dimension of suitable dosage being blocked to each thunder or its and pharmaceutically can connect the salt and the aspirin that draw and be used in combination, can reach the curative effect of better antiplatelet aggregation and thrombosis, and do not increase the bleeding risk of medicine, both couplings have produced good coordinating effect, have obtained beyond thought effect.
The invention provides and contain dimension card Gray or its pharmaceutically acceptable salt and the aspirin Pharmaceutical composition as effective ingredient, dimension card Gray or its pharmaceutically acceptable salt and aspirin are in the application of preparing in Pharmaceutical composition (especially for the Pharmaceutical composition that prevents or treat the disease being caused by thrombosis), the method of the disease that the effective dose prevention in the pharmacology of dimension card Gray or its pharmaceutically acceptable salt and aspirin or treatment are caused by thrombosis, and by dimension card Gray or its pharmaceutically acceptable salt and aspirin simultaneously or give when different with Pharmaceutical composition for preventing or treat the pharmaceutical usage of the disease being caused by thrombosis.
One dimension card Gray or its pharmaceutically acceptable salt of effective ingredient of the present invention are known compounds, are recorded in Chinese patent application 201010104091.5 and 201010624329.7.Its chemical structural formula is as follows.
Dimension card Gray's pharmaceutically acceptable salt can be such as hydrochlorate, hydrobromate, hydriodate, nitrate, perchlorate, sulfate, phosphate, mesylate, trifluoro acute pyogenic infection of nails sulfonate, esilate, benzene sulfonate, tosilate, acetate, malate, fumarate, succinate, citrate, tartrate, oxalates, maleate, lactate, mandelate, pamoic acid (palmoxiric acid) salt, glycinate, lysinate, arginine salt, ornithine salt, glutamate, Glu or aspartate.
Effective ingredient dimension card Gray of the present invention or its pharmaceutically acceptable salt, by being positioned in atmosphere, can absorb moisture or adsorbed water in addition, form hydrate, and such hydrate is also contained in the present invention.
In addition, effective ingredient dimension card Gray of the present invention or its pharmaceutically acceptable salt can absorb certain organic solvent, form solvate, and such solvate is also contained in the present invention.
Another effective ingredient aspirin, as dipron, has been well-known medicine.
The dimension each thunder of card or its pharmaceutically acceptable salt and aspirin of containing provided by the invention has good platelet aggregation inhibitory action and thrombosis inhibitory action as the approximately thing of effective ingredient, and its instant effect, toxicity is little, therefore can be used as preventive or the therapeutic agent of the disease being caused by thrombosis, the disease that described thrombosis causes is stable or unstable angina pectoris, cerebral ischemia attack, the atherosclerosis that the postoperative restenosis of interventional cardiac procedures etc. causes, the thrombotic disease that diabetes occur together, thrombosis after thromboembolism forms disease again, infarction, the dementia that ischemia causes, tip arterial disease, hemodialysis or atrial fibrillation occur together, or blood vessel prosthesis or the thrombotic disease that uses large artery trunks-coronary artery bypass to produce.
In the present composition, in dimension card Gray or its pharmaceutically acceptable salt, free dimension card Gray's parts by weight are 5～150, aspirin parts by weight be 25～300; Preferably, in dimension card Gray or its pharmaceutically acceptable salt, the parts by weight of dimension card Gray free alkali are 10～90, aspirin parts by weight be 50～150; More preferably, in dimension card Gray or its pharmaceutically acceptable salt, the parts by weight of dimension card Gray free alkali are 10～25, aspirin parts by weight be 75～100, by crossing approximately effect, learn experiment discovery in this preferred proportion, dimension card Gray or its pharmaceutically acceptable salt and aspirin use in conjunction synergy are best, anticoagulant effect more effectively, rapidly, hemorrhage rate is down to minimum simultaneously, bleeding risk reduces greatly, has improved overall curative effect and patient compliance in treatment thrombotic disease.
According to the present invention, compared with using separately respectively with dimension card Gray or aspirin, suitably the dimension card Gray of dosage or salt and the aspirin drug combination that it is pharmaceutically accepted demonstrate better antiplatelet aggregation curative effect.In addition, even if 2 kinds of medicaments are not to exist and can reach such effect yet in vivo simultaneously.That is to say, even if 2 kinds of medicaments are not to have above to a certain degree blood drug level simultaneously, also can display effect.By inference, if 2 kinds of medicaments that the present invention uses are all absorbed by body, arrive receptor, play the effect of opening " switch " in body, thereby along with the continuity of the time after administration, even if blood drug level has not shown effect, in fact " switch " opened, and the curative effect of the disease that the prevention that wherein a kind of material has or treatment are caused by thrombosis is proved effective.In this state, give and alternative medicament, in the prevention of the disease being caused by thrombosis or the basis of therapeutic effect having at this medicament, with previously gave with the effect of medicament be added, obtain excellent effect.Certainly, give clinically simultaneously with two kinds approximately agent be easily, therefore, dimension card Gray or its pharmaceutically acceptable salt and aspirin can be with the form administrations of intermixture.If on pharmaceutical technology not preferably by two kinds of medicaments physical mixed simultaneously, so also can be by the administration simultaneously of each single dose.In addition, as mentioned above, when 2 kinds of medicaments are different, give and also can play good effect; Therefore, also can be by each single dose with the successively administration in succession of suitable interval.Reach the maximum dosing interval of 2 kinds of medicaments that the good effect brought by described 2 kinds of medicaments allows, can by clinically or zoopery determine.
The dimension card Gray who uses in the present invention or the route of administration of its pharmaceutically acceptable salt and aspirin are generally oral administration.But cross the route of administration that also can use other, such as intravenously administrable approach etc.Therefore, 2 kinds of medicaments can be prepared and become independent separately unit dosage forms, or form a unit dosage forms physically after mixing.As follows, such unit dosage forms can according to common restriction technology preparation, for example, can be tablet, capsule, slow releasing tablet, granule, powder, syrup, oral liquid or injection.
These preparations can be used following additives, prepare: excipient (for example: lactose according to well-known method, sucrose, glucose, mannitol, Sorbitol, corn starch, potato starch, α starch, dextrin, crystalline cellulose, arabic gum, glucosan, Pullulan, light silicon anhydride, synthetic aluminium silicate, calcium silicates, aluminosilicate magnesium, calcium hydrogen phosphate, calcium carbonate, calcium sulfate), lubricant (for example: stearic acid, calcium stearate, magnesium stearate, Pulvis Talci, Cera Flava, spermaceti, boric acid, adipic acid, sodium sulfate, ethylene glycol, fumaric acid, sodium benzoate, DL leucine, sodium lauryl sulphate, Stepanol MG, silicic acid anhydride, hydrate of silicic acid), binding agent (for example: hydroxypropyl cellulose, hydroxypropyl emthylcellulose, polyvinylpyrrolidone, Polyethylene Glycol, and the compound identical with above-mentioned excipient), disintegrating agent (for example: low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, carboxymethylcellulose calcium, internal crosslinking sodium carboxymethyl cellulose, carboxymethyl starch, carboxymethyl starch sodium, crospolyvinylpyrrolidone, or above-mentioned starch derivatives), emulsifying agent (for example: bentonite, the bond clays such as v word glue, magnesium hydroxide, aluminium hydroxide, sodium lauryl sulphate, calcium stearate, benzalkonium chloride, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid esters, sucrose fatty acid ester), stabilizing agent (for example: methyl parahydroxybenzoate, propyl p-hydroxybenzoate, chlorobutanol, benzyl alcohol, phenethanol, benzalkonium chloride, phenol, cresol, thimerosal, dehydroactic acid, sorbic acid), correctives (for example: sweeting agent, acidic flavoring agent, spice) and diluent etc.
The dimension card Gray who uses in the present invention or the dosage scope of its pharmaceutically acceptable salt and aspirin and administration ratio are that the pharmacokinetics and the pharmacodynamic study that according to the inventor, carry out are determined, also can change according to various conditions such as the activity of each medicament, patient's symptom, age, body weight.
As, in pharmaceutical composition of the present invention, as 5～150 milligrams, the dosage range of aspirin is 25～300 milligrams to the dosage range (to tie up card Gray free alkali) of dimension card Gray or its pharmaceutically acceptable salt; Preferably, dimension card Gray or its are approximately learned the dosage range (to tie up card Gray free alkali) of acceptable salt, as 10～90 milligrams, the dosage range of aspirin are 50～150 milligrams; More preferably, the dosage range (to tie up card Gray free alkali) of dimension card Gray or its pharmaceutically acceptable salt is as 10～25 milligrams, the dosage range of aspirin is 75～100 milligrams, within the scope of this preferred dose, dimension card Gray or its curative effect of approximately learning acceptable salt and aspirin coupling antiplatelet aggregation and thrombosis are best, and do not increase the bleeding risk of about thing.
The specific embodiment
Below by specific embodiment, content of the present invention is described.In the present invention, the embodiment of the following stated is in order better to set forth the present invention, rather than is used for limiting the scope of the invention.
In practical application of the present invention, when use contains the solid preparation (being so-called fixed dosage combination) of tieing up card Gray and aspirin, can adopt following preparation method preparation.
(1) after tieing up card Gray and aspirin and additive (as excipient etc.) and mixing, by granulating mixture, use dispersant or solution (as the binding agent in the water) spraying of additive simultaneously.Gained granule is mixed with additive (as disintegrating agent and lubricant), and then, optionally tabletting is to prepare solid preparation.
(2) will tie up card Gray and additive as mixed with excipients after, by granulating mixture, use dispersant or the solution spray of aspirin simultaneously.Gained granule is mixed with additive (as disintegrating agent and lubricant), and then, optionally tabletting is to prepare solid preparation.
(3) will tie up card Gray and additive as mixed with excipients after, by granulating mixture, use the dispersant of additive or solution (as the binding agent in water) spraying simultaneously.On the other hand, after aspirin is mixed with additive (as excipient), by granulating mixture, use dispersant or solution (as the binding agent in the water) spraying of additive simultaneously.The granule that contains dimension card Gray obtaining thus and the granule that contains aspirin are mixed with additive (as disintegrating agent and lubricant), and then, optionally tabletting is to prepare solid preparation.
(4) will tie up card Gray and additive as mixed with excipients after, by granulating mixture, use the dispersant of additive or solution (as the binding agent in water) spraying simultaneously.On the other hand, the dispersant of aspirin and additive or solution (as the binding agent in water) are sprayed with pelletize.The granule that contains dimension card Gray obtaining thus and the granule that contains aspirin are mixed with additive (as disintegrating agent and lubricant), and then, optionally tabletting is to prepare solid preparation.
(5) will tie up card Gray and additive as mixed with excipients after, by granulating mixture, use the dispersant of additive or solution (as the binding agent in water) spraying simultaneously.Obtained granule is mixed obtain the powder of mixing with additive (as disintegrating agent and lubricant).On the other hand, the dispersant of aspirin and additive or solution (as the binding agent in water) are sprayed with pelletize.Obtained granule is mixed obtain the powder of mixing with additive (as disintegrating agent and lubricant).By the mixed-powder that contains dimension card Gray obtaining thus and the mixed-powder layering that contains aspirin, then compress to prepare solid preparation (two-layer tablet).
(6) will tie up card Gray and additive as mixed with excipients after, by granulating mixture, use the dispersant of additive or solution (as the binding agent in water) spraying simultaneously.Obtained granule is mixed with additive (as disintegrating agent and lubricant), be then pressed into label.On the other hand, the dispersant of aspirin and additive or solution (as the binding agent in water) are sprayed with pelletize.Obtained granule is mixed obtain the powder of mixing with additive (as disintegrating agent and lubricant).The skin that is above-mentioned label by the obtained mixed-powder that contains aspirin pressure is to prepare solid preparation (dry coated tablet).
(7) will tie up card Gray and additive as mixed with excipients after, by granulating mixture, use the dispersant of additive or solution (as the binding agent in water) spraying simultaneously.Obtained granule is mixed with additive (as disintegrating agent and lubricant), be then pressed into sheet.With this sheet of film solution coating of aspirin, coated substrate and additive (as lucifuge agent) to prepare solid preparation (film-coated tablet).
Embodiment 1
The antithrombotic acitivity research of dimension card Gray and aspirin drug combination
Laboratory animal is SD male rat in 7 week age, body weight 250g left and right, and every group is 6.
Dimension card Gray adopts the method preparation of recording in Chinese patent application 201010104091.5 and 201010624329.7, with the form administration of its free alkali.Aspirin is used the product purchased from Sigma Chemical Co..Two kinds of compounds are suspended in the gumwater of 5% (w/v), each laboratory animal is suitably diluted and oral administration administration according to 1ml/kg.Blank group gives the gumwater of isopyknic 5% (w/v).
Adopt the modification method of the rat arteriovenous shut thrombus model (Thromb.Haemost.1978,39,74-83) of bibliographical information to evaluate the anti thrombotic action of tested about thing.Shunt valve is made as follows: will be coated the polyethylene tube (internal diameter: 0.5mm of 7cm silica gel; External diameter: 1.0mm) by the medical silicone tube (internal diameter: 1.0mm of the 0.7cm as adapter; External diameter: 1.5mm), be connected to the medical silicone tube (internal diameter: 1.5mm of long 12cm; External diameter: 2.5mm) two ends.The operation silk thread of long 10cm is set in the silica gel tube of 12cm.By making each laboratory animal anesthesia with 40mg/kg intraperitoneal injection pentobarbital sodium, make it expose the carotid artery of jugular vein and offside.The shunt valve that to fill with heparin solution (30 units/kg) inserts, and forms arteriovenous shut.
By tested about thing oral administration give with, after 2 hours, blood is started at bypass internal recycle.Blood circulation starts, after 30 minutes, to take down shunt valve, measures the thrombus weight being attached on silk thread.Result is as shown in table 1.
Anti thrombotic action when table 1. dimension card Gray and aspirin difference are used alone or in combination
Result of study shows, compared with using separately respectively, ties up card Gray and combines with aspirin with approximately demonstrating better antithrombotic curative effect with dimension card Gray or aspirin.
Embodiment 2
The comparative study of the antiplatelet aggregative activity of dimension card Gray/aspirin drug combination and clopidogrel/aspirin drug combination
Laboratory animal is SD male rat in 7 week age, body weight 250g left and right, and every group is 6.Dimension card Gray is with the form administration of free alkali.Clopidogrel sulfate adopts the product purchased from Sigma Chemical Co..Test-compound with 0.5%CMC-Na (sodium carboxymethyl cellulose) be made into suspension for animal oral give approximately.
Instrument: centrifuge (80-2 table-type low-speed centrifuge) and full-automatic platelet aggregation analyzer (STELLEX LG-PAPER-1 platelet blood coagulation analysis of agglomeration instrument) etc.
Method: with reference to BORN turbidimetry (Nature, 1962,194 (4832): 927), test-compound is carried out to the pact reason activity test of antiplatelet aggregation.To being rich in hematoblastic blood plasma (PRP), add coagulant polymers adenosine diphosphate (ADP) (ADP) to stir, make platelet aggregation.Hematoblastic gathering causes the variation of optical density, can detect by spectrophotometer.The platelet aggregation that this experiment can be evaluated test-compound in vivo or treated in vitro causes.
Platelet aggregation inhibitory activity test: male SD rat per os gavage gives test-compound (unit for uniform suspension of 0.5%CMC-Na, about substrate concentration is 2mg/ml), and blank group per os gavage gives the 0.5%CMC-Na of same volume.The impact of the about thing of hematometry on ADP induced platelet aggregation rate got in administration after 2 hours.Through eye socket, get blood, 3.8% sodium citrate anticoagulant, whole blood is 9:1 with the ratio of anticoagulant, the centrifugal 7mmin of 1000rpm prepares platelet rich plasma (PRP).With platelet poor plasma (PPP), adjust PRP, make platelet count remain on 2 × 106/ml.Get PRP and add in test cup, hatch 10min for 37 ℃, with PRP zeroing, PPP adjusts 100%, take ADP (final concentration is as 5 μ M) as derivant, by turbidimetry, with platelet aggregation instrument, measures platelet aggregation percent, with t-check, carries out statistics comparison.Platelet aggregation inhibition rate is calculated as follows: platelet aggregation inhibition rate (%)=[1-(assembling percentage rate/control tube gathering percentage rate to approximately pipe)] × 100%.Result is as shown in table 2.
The antiplatelet aggregative activity comparison of table 2. dimension card Gray/aspirin drug combination and clopidogrel/aspirin drug combination
Result of study shows, ties up card Gray (3mg/kg)/aspirin (10mg/kg) drug combination and than Gray (10mg/kg)/aspirin (10mg/kg) drug combination, has more significant platelet aggregation inhibitory activity than chlorine; And dimension card Gray (1.5mg/kg)/aspirin (10mg/kg) drug combination has the platelet aggregation inhibitory activity of phase than Gray (10mg/kg)/aspirin (10mg/kg) drug combination with chlorine.Therefore, dimension card Gray/aspirin drug combination is compared with clopidogrel/aspirin drug combination, and the former demonstrates better antiplatelet aggregation curative effect.
Embodiment 3
Tablet
Crude drug is sieved, take after recipe quantity lactose and corn starch mix and add magnesium stearate, direct compression process tabletting, makes the tablet of every 250mg.This tablet can carry out film coating or sugar coating as required.
Embodiment 4
Tablet
The powder of upper table formula is mixed, by tablet machine tabletting, make the tablet of every 250mg.This tablet can carry out film coating or sugar coating as required.
Embodiment 5
Tablet
First listed upper table prescription aspirin is mixed homogeneously with lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, after swelling in hydroxypropyl emthylcellulose purified water, add above-mentioned mixed-powder soft material processed, and granulate, dry, granulate, adds magnesium stearate mix homogeneously; Get dimension card Gray, microcrystalline Cellulose, mannitol, low-substituted hydroxypropyl cellulose mix homogeneously again, add water soft material processed, granulate, dry, granulate, adds castor oil hydrogenated, mix homogeneously.Above-mentioned two parts granule is carried out respectively to tabletting, make double-layer tablet.Again double-layer tablet is carried out to coating, weightening finish 3-5%.
Embodiment 6
Granule
Two parts granule in embodiment 5 is mixed, after mix homogeneously, is filled with in suitable capsule.
Claims (14)
1. approximately use a compositions, described Pharmaceutical composition contains dimension card Gray or its pharmaceutically acceptable salt and aspirin as effective ingredient.
2. the Pharmaceutical composition of claim 1, wherein said pharmaceutically acceptable salt is the acid-addition salts that dimension card Gray and following acid form: hydrochloric acid, hydrobromic acid, sulphuric acid, citric acid, tartaric acid, phosphoric acid, lactic acid, acetic acid, maleic acid, fumaric acid, malic acid, mandelic acid, methanesulfonic acid, benzenesulfonic acid, p-methyl benzenesulfonic acid, pamoic acid, oxalic acid or succinic acid.
3. the Pharmaceutical composition of claim 1, in wherein said compositions, in dimension card Gray or its pharmaceutically acceptable salt, free dimension card Gray's parts by weight are 5～150, aspirin parts by weight be 25～300.
4. the Pharmaceutical composition of claim 1, in wherein said compositions, in dimension card Gray or its pharmaceutically acceptable salt, free dimension card Gray's parts by weight are 10～90, aspirin parts by weight be 50～150.
5. the Pharmaceutical composition of claim 1, in wherein said compositions, in dimension card Gray or its pharmaceutically acceptable salt, free dimension card Gray's parts by weight are 10～25, aspirin parts by weight be 75～100.
6. the Pharmaceutical composition of claim 1, wherein said pharmaceutical composition is tablet, capsule, slow releasing tablet, granule, powder, syrup, oral liquid or injection.
7. the Pharmaceutical composition of claim 6, wherein said tablet, capsule, slow releasing tablet or granule comprise as the dimension card Gray of effective ingredient or the compartment of its pharmaceutically acceptable salt with as the compartment of the aspirin of effective ingredient.
8. the purposes in prevention or the medicine of the disease that the compositions of claim 1 is caused by thrombosis in preparation.
9. the purposes of claim 8, the thrombotic disease that the thrombosis of described medicine after for thrombotic disease, the thromboembolism of preventing or treating atheromatosis, stable or unstable angina pectoris, cerebral ischemia attack, diabetes and occurring together forms that dementia, tip arterial disease, hemodialysis or atrial fibrillation that disease, infarction, ischemia cause occur together or blood vessel prosthesis again or use large artery trunks coronary artery bypass to produce.
10. the purposes of claim 8, wherein said medicine be simultaneously to the form of medicinal drug.
The purposes of 11. claim 8, wherein said medicine be successively in succession to the form of medicinal drug.
The purposes of 12. claim 8, wherein dimension card Gray or its are approximately learned the dosage range (to tie up card Gray free alkali) of acceptable salt, as 5～150 milligrams, the dosage range of aspirin are 25～300 milligrams.
The purposes of 13. claim 8, wherein as 10～90 milligrams, the dosage range of aspirin is 50～150 milligrams to the dosage range (to tie up card Gray free alkali) of dimension card Gray or its pharmaceutically acceptable salt.
The purposes of 14. claim 8, wherein as 10～25 milligrams, the dosage range of aspirin is 75～100 milligrams to the dosage range (to tie up card Gray free alkali) of dimension card Gray or its pharmaceutically acceptable salt.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310435324.3A CN103720700A (en) | 2012-10-10 | 2013-09-24 | Medical composition containing aspirin and vicagrel |
| PCT/CN2013/084815 WO2014056418A1 (en) | 2012-10-10 | 2013-10-07 | Pharmaceutical composition containing aspirin and vicagrel |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210382331 | 2012-10-10 | ||
| CN201210382331.7 | 2012-10-10 | ||
| CN201310435324.3A CN103720700A (en) | 2012-10-10 | 2013-09-24 | Medical composition containing aspirin and vicagrel |
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| Publication Number | Publication Date |
|---|---|
| CN103720700A true CN103720700A (en) | 2014-04-16 |
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| CN201310435324.3A Pending CN103720700A (en) | 2012-10-10 | 2013-09-24 | Medical composition containing aspirin and vicagrel |
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| WO (1) | WO2014056418A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019200512A1 (en) | 2018-04-16 | 2019-10-24 | 江苏威凯尔医药科技有限公司 | Instant release pharmaceutical preparation of anticoagulant and preparation method therefor |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2744918B1 (en) * | 1996-02-19 | 1998-05-07 | Sanofi Sa | NEW COMBINATIONS OF ACTIVE INGREDIENTS CONTAINING THIENO (3,2-C) PYRIDINE DERIVATIVE AND AN ANTITHROMBOTIC |
| CN102863457B (en) * | 2010-02-02 | 2013-10-09 | 江苏威凯尔医药科技有限公司 | Optically-active 2- hydroxyltetrathienopyridine derivative, preparation method thereof and application of optically-active 2- hydroxyltetrathienopyridine derivative to pharmacy |
| NZ606903A (en) * | 2010-08-26 | 2015-05-29 | Ipca Lab Ltd | Methods for the treatment or prophylaxis of thrombosis or embolism |
| CN102228691A (en) * | 2011-06-29 | 2011-11-02 | 北京阜康仁生物制药科技有限公司 | Aspirin and anticoagulant pharmaceutical composition |
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| WO2019200512A1 (en) | 2018-04-16 | 2019-10-24 | 江苏威凯尔医药科技有限公司 | Instant release pharmaceutical preparation of anticoagulant and preparation method therefor |
| KR20210015788A (en) * | 2018-04-16 | 2021-02-10 | 지앙수 브이케어 파마테크 컴퍼니 리미티드 | Rapid release drug formulation of anticoagulant and method for manufacturing same |
| JP2021523094A (en) * | 2018-04-16 | 2021-09-02 | チャンスー ヴィーケア ファーマテック カンパニー リミテッド | Immediate release of anticoagulant Pharmaceutical preparation and its preparation method |
| US11478432B2 (en) | 2018-04-16 | 2022-10-25 | Jiangsu Vcare Pharma Tech Co., Ltd. | Instant release pharmaceutical preparation of anticoagulant and preparation method therefor |
| JP7218949B2 (en) | 2018-04-16 | 2023-02-07 | チャンスー ヴィーケア ファーマテック カンパニー リミテッド | Immediate release pharmaceutical formulation of anticoagulant and method for its preparation |
| JP2023052494A (en) * | 2018-04-16 | 2023-04-11 | チャンスー ヴィーケア ファーマテック カンパニー リミテッド | Instant release pharmaceutical preparation of anticoagulant and preparation method therefor |
| KR102627892B1 (en) * | 2018-04-16 | 2024-01-22 | 지앙수 브이케어 파마테크 컴퍼니 리미티드 | Rapid release drug formulation of anticoagulant and method for manufacturing same |
| US11878078B2 (en) | 2018-04-16 | 2024-01-23 | Jiangsu Vcare Pharmatech Co., Ltd. | Instant release pharmaceutical preparation of anticoagulant and preparation method therefor |
| JP7428836B2 (en) | 2018-04-16 | 2024-02-06 | チャンスー ヴィーケア ファーマテック カンパニー リミテッド | Immediate release pharmaceutical formulation of anticoagulant and method for its preparation |
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| WO2014056418A1 (en) | 2014-04-17 |
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