CN102949357A - Prasugrel hydrobromide tablet - Google Patents
Prasugrel hydrobromide tablet Download PDFInfo
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- CN102949357A CN102949357A CN2011102361994A CN201110236199A CN102949357A CN 102949357 A CN102949357 A CN 102949357A CN 2011102361994 A CN2011102361994 A CN 2011102361994A CN 201110236199 A CN201110236199 A CN 201110236199A CN 102949357 A CN102949357 A CN 102949357A
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- prasugrel
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Abstract
The invention relates to a Prasugrel hydrobromide tablet suitable for preparation by a direct compression process. In addition to containing the active component Prasugrel hydrobromide, the tablet also contains a filling agent, a disintegrating agent and a lubricant. And the tablet has the advantages of high dissolution rate, good stability, high safety, and simple preparation process.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be in particular a kind of tablet of prasugrel hydrobromide.
Background technology
Prasugrel is come by U.S.'s macro-organism pharmacy corporation gift at first and Japanese the first pharmacy three is total to cooperation research and development.It is a kind of adenosine diphosphate (ADP) receptor antagonist, and as anticoagulant, it belongs to prodrug, itself does not have activity, changes in vivo its active metabolite R-138727; R-138727 has reduced the dependency to the cytochrome P-450 enzyme, and rapidly, special, the irreversible purine bases receptor that is attached to platelet P2Y12, suppress ADP and regulate hematoblastic activity and gathering.Needing to be mainly used in the syndromic patient of percutaneous coronary, to comprise the patient that need to carry out stent endoprosthesis.
Usually, use the pharmaceutically acceptable salt of medicinal compound, United States Patent (USP) 6693115B2 discloses the preparation of hydrochlorate and the maleate of prasugrel, the form of these two kinds of salt is all having in various degree raising aspect their stability and the drug effect, its hydrochlorate preparation is at America and Europe's listing, trade name Efient.
Prasugrel hydrobromide, molecular formula: C
20H
20FNO
3SHBr, molecular weight: 454.3, structural formula is as follows:
Patent WO2008073759 points out that prasugrel is easy to hydrolysis and oxidation in storing process, although the stability of the hydrobromate of prasugrel has improvement to a certain degree, but still not fully up to expectations.
Chinese invention patent application CN101804042 discloses a kind of preparation method of prasugrel tablets; its technical scheme prepares label by tabletting exactly; coat the gastric solubility protective layer that contains antioxidant at label again; can also coat the gastric solubility film-coat outside containing the gastric solubility protective layer of antioxidant, its purpose is to guarantee by adding anti oxidation layer the stability of prasugrel again.Its shortcoming is that antioxygen layer can only reduce the oxidation of prasugrel, and the hydrolyzate that affects of the factor such as damp and hot increases faster on the contrary in the coating process; Complicated process of preparation; There is potential harm in the application of simultaneously a large amount of antioxidant, coloring agent to human body.
Chinese invention patent application CN101568339 discloses the goods of prasugrel, its tablet, caplets, capsule or other solid dosage forms that is included under the positive liquefied gas pressure prasugrel is packaged in air and/or the impervious container of dampness, solve the stability problem of prasugrel with this, the production operation difficulty is large, and cost is high.
Chinese invention patent application CN101919823 discloses a kind of Pharmaceutical composition for the treatment of thrombosis, its technical scheme is that this Pharmaceutical composition contains prasugrel hydrobromide 5-20mg and pharmaceutically acceptable adjuvant thereof, and the form with coated tablet exists, inevitably use water or other nonaqueous solvent in the coating process and need heating, solvent for use also all can have residual, these factors all can be accelerated hydrolysis and the oxidation of prasugrel, cause tablet unstable.In addition, in this patent the prepared tablet stripping of embodiment too slow, stripping curve and external listing preparation (Efient) and dissimilar (f
2＜50).
Summary of the invention
For exploitation is used for prevention or treatment people's thrombosis or the more stable effective medicine of the disease that thromboembolism causes, the inventor carries out deep for a long time research by the physicochemical properties to prasugrel hydrobromide, on a large amount of experimental basis, screen and prepared more stable, bioavailability better, the higher tablet of safety.
The selected adjuvant of the present invention, all by the screening of supplementary material compatibility test, stability is significantly better than other adjuvant.Adopt the tablet stability of the selected adjuvant preparation of the present invention good, need of coating or employing extra package can not guarantee the stability of tablet.Simultaneously, selected supplementary product kind is less and be adjuvant commonly used, and drug safety is better.
The flowability of the selected filler of the present invention better is fit to the requirement of direct compression.Therefore, prasugrel hydrobromide sheet preparation technology of the present invention is more simple, has avoided causing in the wet-granulation process increase of prasugrel hydrobromide related substance.
The present invention also screens filler loading.Find in the test that filler loading is more, mobility of particle is better, and uniformity of dosage units is better; But it is unfavorable that too much or very few filler is related substance stability.Filler loading very little, mobility of particle is poor, the sheet uniformity of dosage units is relatively poor, can find out that by Comparative Examples 3 its uniformity of dosage units obviously is worse than embodiment.Filler loading is too much or very few, and tablet stability is relatively poor, can find out that by Comparative Examples 3,4 its stability obviously is worse than embodiment; And most preferred embodiment 11,12 obviously is better than other embodiment; Preferred embodiment 8～10,13,14 also is better than embodiment 1～7.
The present invention also screens the disintegrating agent consumption.The disintegrating agent consumption very little or too much, it is unfavorable that stripping is.Can find out that by Comparative Examples 3,4 its dissolution is all poor than embodiment; And most preferred embodiment 11,12 and preferred embodiment 8～10,13,14 also embodied its superiority aspect stripping.
The present invention adopts following technical scheme:
A kind of tablet of prasugrel hydrobromide except containing the active component prasugrel hydrobromide, also contains filler, disintegrating agent and lubricant.
Prasugrel hydrobromide is in free alkali, and described tablet contains the component of following weight ratio:
Preferably, the weight ratio of each component is:
More preferably, the weight ratio of each component is:
Described filler is one or more in starch milk saccharide complex, optimization microcrystalline Cellulose, sorbitol (Neosorb), betacyclodextrin (Kleptose), pregelatinized Starch, microcrystalline Cellulose, lactose, mannitol, the calcium hydrogen phosphate.
Described disintegrating agent is selected from one or more in crospolyvinylpyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, the low-substituted hydroxypropyl cellulose.
Described lubricant is selected from one or more in sodium stearyl fumarate, magnesium stearate, zinc stearate, calcium stearate, hydrogenated vegetable oil, the micropowder silica gel.
Prasugrel hydrobromide tablets of the present invention, adopt the method preparation of direct compression, concrete preparation technology is: prasugrel hydrobromide is crossed 120 mesh sieves, gets sieve prasugrel hydrobromide and disintegrating agent, filler by the equivalent mix homogeneously that progressively increases, add the lubricant mixing, tabletting.
Prasugrel hydrobromide tablets of the present invention is more stable, bioavailability is better.Can find out that by test example 1 tablet stability of the present invention is good, and dissolution is high, preparation technology is simple.Can find out that by test example 2 prasugrel hydrobromide tablets bioavailability of the present invention is good, and is better than Comparative Examples.Therefore, prasugrel hydrobromide tablets of the present invention has outstanding advantage, and technique is simple, is applicable to large-scale production.
The specific embodiment
Come prasugrel hydrobromide tablets of the present invention is described further by following examples, but the present invention is not limited in following examples.
Embodiment 1
Preparation method: prasugrel hydrobromide is crossed 120 mesh sieves, get recipe quantity and sieved prasugrel hydrobromide and recipe quantity starch milk saccharide complex by the equivalent mix homogeneously that progressively increases, add recipe quantity magnesium stearate mix homogeneously, measure semi-finished product content, the calculating sheet is heavy, tabletting and get final product.
Embodiment 2
Preparation method is with embodiment 1.
Embodiment 3
Preparation method is with embodiment 1.
Embodiment 4
Preparation method is with embodiment 1.
Embodiment 5
Preparation method is with embodiment 1.
Embodiment 6
Preparation method is with embodiment 1.
Embodiment 7
Preparation method is with embodiment 1
Embodiment 8
Preparation method is with embodiment 1.
Embodiment 9
Preparation method is with embodiment 1.
Embodiment 10
Preparation method is with embodiment 1.
Embodiment 11
Preparation method is with embodiment 1.
Embodiment 12
Preparation method is with embodiment 1.
Embodiment 13
Preparation method is with embodiment 1.
Embodiment 14
Preparation method is with embodiment 1.
Comparative Examples 1
Preparation method:
1. prasugrel hydrobromide and mannitol, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, hypromellose equivalent are progressively increased, mix homogeneously gets mixture 1;
2. mixture 1 is carried out dry granulation and get granule 1;
3. magnesium stearate is joined in the granule 1 that makes mix homogeneously;
4. with the hybrid particles compress tablet coating.
Comparative Examples 2
Preparation method:
1. prasugrel hydrobromide and mannitol, microcrystalline Cellulose, cross-linked carboxymethyl cellulose sodium, hypromellose equivalent are progressively increased, mix homogeneously gets mixture 1;
2. mixture 1 is carried out dry granulation and get granule 1;
3. Glyceryl Behenate, sucrose stearate are joined in the granule 1 that makes mix homogeneously;
4. with the hybrid particles compress tablet coating.
Embodiment 3
Preparation method: prasugrel hydrobromide is crossed 120 mesh sieves, get recipe quantity and sieved prasugrel hydrobromide and recipe quantity starch milk saccharide complex by the equivalent mix homogeneously that progressively increases, add recipe quantity magnesium stearate mix homogeneously, measure semi-finished product content, the calculating sheet is heavy, tabletting and get final product.
Comparative Examples 4
Preparation method is with Comparative Examples 3.
Test example 1 embodiments of the invention have following technical characteristic:
1. uniformity of dosage units
Uniformity of dosage units detection method: measure according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2010).Be filler with octyl silane group silica gel, acetonitrile-0.05mol/L citric acid (70: 30) is mobile phase, detects wavelength 220nm.Theoretical cam curve is not less than 2000 by prasugrel.
Get this product a slice, place the 100ml measuring bottle, make dissolving with acetonitrile is ultrasonic, let cool, be diluted to scale, shake up, filter with 0.45 μ m filter membrane, get subsequent filtrate and make need testing solution; It is an amount of that other gets prasugrel hydrobromide, accurately weighed, adds acetonitrile and make every 1ml and contain prasugrel (C
20H
20FNO
3S) solution of 0.1mg, in contrast product solution.Precision is measured respectively injection liquid chromatography of each 20 μ l of need testing solution and reference substance solution, with the content of external standard method with the calculated by peak area prasugrel hydrobromide, and should (two appendix XE of Chinese Pharmacopoeia version in 2010) up to specification.
The uniformity of dosage units of table 1 prasugrel hydrobromide tablets
As shown in Table 1, filler loading is more, and uniformity of dosage units is better.Comparative Examples 3 filler loadings are less than consumption of the present invention, the obvious variation of uniformity of dosage units.
2. dissolution
To carry out dissolution comparative study by tablet and the Comparative Examples of embodiment of the invention preparation.
Measure according to dissolution method (2010 editions two appendix XC the second methods of Chinese Pharmacopoeia).Get the embodiment of the invention 1～14 and Comparative Examples 1～4 sample each 6, take pH1.2 hydrochloric acid 900ml as dissolution medium, rotating speed is 50 rev/mins, in accordance with the law the operation, got solution respectively at 5,10,15,30 minutes and filter in right amount, as need testing solution; In addition to take by weighing prasugrel hydrobromide an amount of for precision, puts in the measuring bottle, adds that acetonitrile is an amount of ultrasonicly to make dissolving, and be diluted to suitable concentration with dissolution medium, in contrast product solution.Precision is measured need testing solution and each 20 μ l difference injection liquid chromatography of reference substance solution, and the method for pressing under the assay item is measured, and the results are shown in Table 2:
Table 2 prasugrel hydrobromide tablets stripping comparative study
As shown in Table 2, be that the 15Min dissolution obviously is better than Comparative Examples all more than 85% in 1.2 the hydrochloric acid by the tablet of embodiment of the invention preparation at pH; And most preferred embodiment 11,12 obviously is better than other embodiment; Preferred embodiment 8～10,13,14 also is better than embodiment 1～7.
3. content
Will be by the tablet of embodiment of the invention preparation and the stability under Comparative Examples contrast acceleration (40 ℃ 75%) condition.
Detection method of content is: according to high performance liquid chromatography (2010 editions two appendix VD of Chinese Pharmacopoeia)
Chromatographic condition and system suitability test are filler with octyl silane group silica gel, and acetonitrile-0.05mol/L citric acid (70: 30) is mobile phase, detect wavelength 220nm.Theoretical cam curve is not less than 2000 by prasugrel.
The fine powder that algoscopy is got this product (is equivalent to C in right amount approximately
20H
20FNO
3S 10mg), puts in the 100ml measuring bottle, make dissolving with acetonitrile is ultrasonic, let cool, be diluted to scale, shake up, filter with 0.45 μ m filter membrane, get subsequent filtrate and make need testing solution; It is an amount of that other gets prasugrel hydrobromide, accurately weighed, adds acetonitrile and make every 1ml and contain prasugrel (C
20H
20FNO
3S) solution of 0.1mg, in contrast product solution.Precision is measured need testing solution and each 20 μ l difference injection liquid chromatography of reference substance solution, with the content of external standard method with the calculated by peak area prasugrel hydrobromide.
The content balance result of study sees Table 3.
Table 3 prasugrel hydrobromide sheet content balance result of study
As shown in Table 3, the stability by the tablet content of embodiment of the invention preparation obviously is better than Comparative Examples; And most preferred embodiment 11,12 is better than other embodiment; Preferred embodiment 8～10,13,14 also is better than embodiment 1～7.
4. related substance
Related substance detection method: according to high performance liquid chromatography (2010 editions two appendix VD of Chinese Pharmacopoeia)
Chromatographic condition and system suitability test are filler with octyl silane group silica gel, and acetonitrile-0.05mol/L citric acid (70: 30) is mobile phase, detect wavelength 220nm.Theoretical cam curve is not less than 4000 by prasugrel.
The fine powder that algoscopy is got this product (is equivalent to C in right amount approximately
20H
20FNO
3S 10mg), puts in the 10ml measuring bottle, make dissolving with acetonitrile is ultrasonic, let cool, be diluted to scale, shake up, filter with 0.45 μ m filter membrane, get subsequent filtrate and make need testing solution; Precision is measured need testing solution 1ml, puts in the 100ml measuring bottle, adds dilution in acetonitrile to scale, compares product solution; Measure contrast solution 20 μ l injection liquid chromatographies, regulate detection sensitivity, the peak height that makes the main constituent peak is 25% of monitor full scale, precision is measured need testing solution and each 20 μ l difference injection liquid chromatography of reference substance solution again, the record chromatogram is to 3 times of prasugrel hydrobromide peak retention time, such as aobvious impurity peaks, each impurity peaks peak area sum must not be greater than the main peak area (1.0%) of reference substance solution in the chromatogram of need testing solution.
Related substance comparative study the results are shown in Table 4.
Table 4 prasugrel hydrobromide sheet related substance comparative study result
As shown in Table 4, the stability by the tablet related substance of embodiment of the invention preparation obviously is better than Comparative Examples; And most preferred embodiment 11,12 obviously is better than other embodiment; Preferred embodiment 8～10,13,14 also is better than embodiment 1～7.
Can be found out by above result, all be better than Comparative Examples 1,2 tablets that prepare by the tablet content uniformity of the present invention preparation, dissolution, stability etc., and preparation technology be simple, is applicable to industrialized great production.
The mensuration of the bioavailability of test example 2 prasugrel hydrobromide tablets of the present invention
1, grouping and administration
28 of healthy male beasle dogs, about 7 months ages, the body weight no difference of science of statistics was normally raised for 2 weeks and is not taken any medicine before the experiment.28 beasle dogs are divided into prasugrel hydrobromide tablets group of the present invention (embodiment 1), Comparative Examples group (Comparative Examples 1), 14 every group at random.
2, index determining
Behind the prasugrel hydrobromide sheet of oral embodiment 1 and Comparative Examples 1, measure the metabolite concentration in the blood plasma.S-methyl body is (2Z)-[1[a-cyclopropyl carbonyl-2-luorobenzyl]-4-methyl mercapto-3-piperidylidene (piperidinylidene) acetic acid, 2-acetoxyl group-5-(a-cyclopropyl carbonyl-2-luorobenzyl)-4,5,6,7-Tetramethylene sulfide also [3,2-c] pyridine is the people, Canis familiaris L., major metabolite in the blood plasma of rat, 2-acetoxyl group-5-(a-cyclopropyl carbonyl-2-luorobenzyl)-4,5,6, the 7-Tetramethylene sulfide also pharmacologically active metabolite of [3,2-c] pyridine produces through further continuous metabolism, so s-methyl body becomes the index of active metabolite growing amount.
Behind the beasle dog feeding 30 minutes, oral test medicine (10mg/kg).After administration 15,30,45,60,90 and 120 minutes, use the syringe of processing through heparin, by upper buttocks saphena blood sampling, 3ml takes a blood sample at every turn.The whole blood that obtains is carried out centrifugalize immediately, obtain blood plasma, the blood plasma that obtains carries out-30 ℃ of freezing preservations before test.To middle 2-hydroxy acetophenone (0.25ml) and 10mM kaliumphosphate buffer (pH4.5,0.25ml) and the methanol (0.5ml) that adds as 1 μ g/ml concentration of interior mark 5 of the blood plasma that thaws (0.5ml), 20 ± 3 ℃ of stirrings.After wherein adding isopropanol/chloroform (1/9) mixed liquor (8ml), vibration is extracted into solvent phase with s-methyl body and internal standard substance.By low-speed centrifugal (1500g, 15 minutes) water is separated with solvent phase, with lower floor's solvent phase of nitrogen drying appropriate amount.It is dissolved in the HPLC mobile phase (0.25ml) again.In addition, the s-methyl body of known quantity is added in the beasle dog contrast blood plasma, carries out same extracting operation.S-methyl body in the sample and the Area Ratio of internal standard substance be as the y axle, take the s-methyl bulk concentration that adds as the x axle, makes calibration curve.Calculate the concentration of s-methyl body in the sample by this calibration curve, thereby quantitatively.
The HPLC condition:
Post: YMC A302 (4.6*150mm).
Mobile phase: acetonitrile/isopropanol/water/trichloroacetic acid (10/12/78/0.01).
Flow velocity: 1.0ml/min.
Detect: UV220nm.
Injection rate: 30 μ l.
The result is as shown in table 5, in the table, as pharmacokinetic parameters, becomes that concentration represents with AUC and Cmax omission respectively in area value under the Plasma-time graph of growing amount index in the body and the maximum plasma.
3, result of the test
Compare with contrast groups, the bioavailability of prasugrel hydrobromide tablets of the present invention in beagle dog body is better than Comparative Examples, and standard deviation is little, and to reflect individual variation little.
The pharmacokinetic parameters of s-methyl body in the blood plasma after the administration of table 5 beagle dog
Claims (7)
1. the tablet of a prasugrel hydrobromide, it is characterized in that: prasugrel hydrobromide is in free alkali, and described tablet contains the component of following weight ratio:
2. the tablet of prasugrel hydrobromide as claimed in claim 1, it is characterized in that: the weight ratio of described each component is:
3. the tablet of prasugrel hydrobromide as claimed in claim 2, it is characterized in that: the weight ratio of described each component is:
4. such as the tablet of prasugrel hydrobromide as described in the claim 1,2 or 3, it is characterized in that: described filler is the starch milk saccharide complex, optimize one or more in microcrystalline Cellulose, sorbitol, betacyclodextrin, pregelatinized Starch, microcrystalline Cellulose, lactose, mannitol or the calcium hydrogen phosphate.
5. such as the tablet of prasugrel hydrobromide as described in the claim 1,2 or 3, it is characterized in that: described disintegrating agent is selected from one or more in crospolyvinylpyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium or the low-substituted hydroxypropyl cellulose.
6. such as the tablet of prasugrel hydrobromide as described in the claim 1,2 or 3, it is characterized in that: described lubricant is selected from one or more in sodium stearyl fumarate, magnesium stearate, zinc stearate, calcium stearate, hydrogenated vegetable oil or the micropowder silica gel.
7. the tablet of prasugrel hydrobromide as described in arbitrary such as claim 1-6, it is characterized in that: adopt the method preparation of direct compression, concrete preparation technology is: prasugrel hydrobromide is crossed 120 mesh sieves, get sieve prasugrel hydrobromide and disintegrating agent, filler by the equivalent mix homogeneously that progressively increases, add the lubricant mixing, tabletting.
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|---|---|---|---|
| CN201110236199.4A CN102949357B (en) | 2011-08-17 | 2011-08-17 | A kind of tablet of prasugrel hydrobromide |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173316A (en) * | 2013-05-22 | 2014-12-03 | 山东新时代药业有限公司 | Capsule of hydrobromic acid prasugrel |
| CN104337784A (en) * | 2013-08-02 | 2015-02-11 | 山东新时代药业有限公司 | Hydrotropic acid prasugrel tablet and preparing method thereof |
| CN105106146A (en) * | 2015-09-02 | 2015-12-02 | 重庆百农网投资有限公司 | Directly-compressed tablet comprising traditional Chinese medicine including lotus seeds and oyster shells |
| CN105310989A (en) * | 2014-07-03 | 2016-02-10 | 重庆安格龙翔医药科技有限公司 | Prasugrel oxalate tablet and preparation method of same |
| CN105435237A (en) * | 2015-12-17 | 2016-03-30 | 河南润弘制药股份有限公司 | Prasugrel hydrochloride pharmaceutical composition, tablets and preparation method of tablets |
| CN106913542A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of prasugrel tablets and preparation method thereof |
| CN107789327A (en) * | 2016-09-07 | 2018-03-13 | 成都康弘药业集团股份有限公司 | A kind of pharmaceutical composition containing hydrobromic acid Wo Saiting and preparation method thereof |
| CN107961221A (en) * | 2016-10-20 | 2018-04-27 | 长春海悦药业股份有限公司 | A kind of pharmaceutical composition containing prasugrel hydrochloride and preparation method thereof |
| CN112057428A (en) * | 2020-10-22 | 2020-12-11 | 上海翰森生物医药科技有限公司 | Pharmaceutical composition of varenicline tartrate and preparation method thereof |
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| WO2009098142A1 (en) * | 2008-02-06 | 2009-08-13 | Helm Ag | Prasugrel salts with improved properties |
| CN101919823A (en) * | 2010-08-02 | 2010-12-22 | 北京德众万全医药科技有限公司 | Medicinal composition for treating thrombus |
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| WO2009098142A1 (en) * | 2008-02-06 | 2009-08-13 | Helm Ag | Prasugrel salts with improved properties |
| CN101919823A (en) * | 2010-08-02 | 2010-12-22 | 北京德众万全医药科技有限公司 | Medicinal composition for treating thrombus |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104173316A (en) * | 2013-05-22 | 2014-12-03 | 山东新时代药业有限公司 | Capsule of hydrobromic acid prasugrel |
| CN104173316B (en) * | 2013-05-22 | 2018-05-18 | 山东新时代药业有限公司 | A kind of capsule of prasugrel hydrobromide |
| CN104337784A (en) * | 2013-08-02 | 2015-02-11 | 山东新时代药业有限公司 | Hydrotropic acid prasugrel tablet and preparing method thereof |
| CN104337784B (en) * | 2013-08-02 | 2018-05-11 | 山东新时代药业有限公司 | A kind of prasugrel hydrobromide tablets and preparation method thereof |
| CN105310989A (en) * | 2014-07-03 | 2016-02-10 | 重庆安格龙翔医药科技有限公司 | Prasugrel oxalate tablet and preparation method of same |
| CN105106146A (en) * | 2015-09-02 | 2015-12-02 | 重庆百农网投资有限公司 | Directly-compressed tablet comprising traditional Chinese medicine including lotus seeds and oyster shells |
| CN105106146B (en) * | 2015-09-02 | 2018-03-30 | 重庆百农网投资有限公司 | Vertical compression tablet containing Chinese medicine lotus seeds and oyster shell |
| CN105435237B (en) * | 2015-12-17 | 2018-12-28 | 河南润弘制药股份有限公司 | A kind of prasugrel hydrochloride pharmaceutical composition, tablet and preparation method thereof |
| CN105435237A (en) * | 2015-12-17 | 2016-03-30 | 河南润弘制药股份有限公司 | Prasugrel hydrochloride pharmaceutical composition, tablets and preparation method of tablets |
| CN106913542A (en) * | 2015-12-28 | 2017-07-04 | 山东新时代药业有限公司 | A kind of prasugrel tablets and preparation method thereof |
| CN106913542B (en) * | 2015-12-28 | 2021-06-04 | 山东新时代药业有限公司 | Prasugrel tablet and preparation method thereof |
| CN107789327B (en) * | 2016-09-07 | 2020-06-02 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing vortioxetine hydrobromide and preparation method thereof |
| CN107789327A (en) * | 2016-09-07 | 2018-03-13 | 成都康弘药业集团股份有限公司 | A kind of pharmaceutical composition containing hydrobromic acid Wo Saiting and preparation method thereof |
| CN107961221A (en) * | 2016-10-20 | 2018-04-27 | 长春海悦药业股份有限公司 | A kind of pharmaceutical composition containing prasugrel hydrochloride and preparation method thereof |
| CN107961221B (en) * | 2016-10-20 | 2020-06-05 | 长春海悦药业股份有限公司 | Pharmaceutical composition containing prasugrel hydrochloride and preparation method thereof |
| CN112057428A (en) * | 2020-10-22 | 2020-12-11 | 上海翰森生物医药科技有限公司 | Pharmaceutical composition of varenicline tartrate and preparation method thereof |
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