CN103467484A - Compound and medicine composition containing micronized prasugrel and salts of prasugrel - Google Patents
Compound and medicine composition containing micronized prasugrel and salts of prasugrel Download PDFInfo
- Publication number
- CN103467484A CN103467484A CN201310388714XA CN201310388714A CN103467484A CN 103467484 A CN103467484 A CN 103467484A CN 201310388714X A CN201310388714X A CN 201310388714XA CN 201310388714 A CN201310388714 A CN 201310388714A CN 103467484 A CN103467484 A CN 103467484A
- Authority
- CN
- China
- Prior art keywords
- prasugrel
- salt
- compound
- micronized
- particle diameter
- 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.)
- Granted
Links
Images
Abstract
The invention relates to a compound and medicine composition containing micronized prasugrel and salts of prasugrel. Prasugrel and the salts of prasugrel are micronized by adopting a superfine grinding technology till the particle sizes of the prasugrel and the prasugrel salts are in the range from 3micrometers to 10 micrometers, thus the micronized compound is obtained. The medicine composition is prepared from the micronized compound of prasugrel and the salts of prasugrel and appropriate auxiliary materials, wherein the weight of prasugrel and the salts of prasugrel accounts for 0.1%-10% of the total weight of the medicine composition. The superfine grinding technology is used for preparing the compound of the prasugrel and salts of the prasugrel and the particle size of the compound is 3 to 10 micrometers, so that the water solubility of the prasugrel and the prasugrel salts is increased, the biological availability is improved, and the clinical effect of the medicinal preparation is improved.
Description
Technical field
The present invention relates to a kind of micronized prasugrel that superfine communication technique makes and product of salt and preparation thereof of adopting, belong to medical technical field.
Background technology
Prasugrel (prasugrel) is a novel antiplatelet drug, in Europe and U.S.'s listing.(clopidogrel) is similar for same clopidogrel, and prasugrel passes through to suppress adenosine diphosphate (ADP) (adenosine diphosphate, ADP) thereby the platelet aggregation of inducing performance antiplatelet effects.But the antiplatelet effects of prasugrel is stronger than clopidogrel, and onset is faster.Prasugrel is thiophene chloropyridine, chlorine pyrrole thunder lattice analogue, 1993 by Japan three altogether, the P2Y12 purinoceptor antagonist with oral property of Ube Industries, Lilly joint development, within 2009, in European Union and FDA, successively ratify listing, it is the lead compound in a series of tetrahydrothieno pyridines analog derivatives, as platelet aggregation inhibitor, with prevention and treatment thrombosis.
The preparation that prasugrel goes on the market abroad at present is tablet, and the prasugrel sheet is mainly used in hospital clinical abroad.Clinical studies show, prasugrel has than the better blood coagulation resisting function of current main flow medicine clopidogrel, simultaneously to heart attack, apoplexy, because the integrated risk of deaths from heart disease is low by 20%, and instant effect, good effect, have good resistance and bioavailability.This kind is the good efficacy in market abroad, will excite its use scale in market at home.
The solvability of prasugrel and salt thereof is poor, causes bioavailability lower, utilizes existing preparation technique to improve its water-soluble, improves bioavailability, becomes the problem of a present hot topic.
Micronizing is nearly new and high technology developed rapidly in 20 years, can be processed into the even nano level micro mist of micron to starting material, in every profession and trade, is widely used.The air-flow superfine communication technique is a kind of of superfine communication technique, it utilizes material under the effect of high velocity air, obtain huge kinetic energy, cause the high velocity impact between material particles, violent friction in crushiing chamber, high velocity air produces shearing action to material simultaneously, thereby reach the purpose of comminuting matter, it can become Raw material processing superfine powder (<10 μ m).But at present, the technician of pharmaceutical field is applied to Chinese medicine by superfine communication technique, up to now, almost superfine communication technique is not applied to pharmaceutical chemicals Western medicine aspect, with the application of the existing defect in preparation aspect of improving pharmaceutical chemicals.
Prior art CN102675338A discloses a kind of micronization prasugrel and has been the pharmaceutical composition of activeconstituents, micronization prasugrel wherein, and the particle diameter at its 90% cumulative volume place is below 25 μ m.
Generally speaking, by to medical compounds crystallization pulverized to there is less particle diameter, contribute to improve the stripping property of medicament, yet, for the solid preparation that contains prasugrel, predict that how the drug microparticles of particle diameter is difficult in order to control stripping property for the professional and technical personnel of this field.
Only by measuring the dissolution rate of pharmaceutical preparation in the hydrochloric acid medium of simulation normal human gastric acid environment, be not enough to predict medicine dissolving out capability and bioavailability in vivo, only make pharmaceutical preparation all there is dissolution characteristic preferably under the multiple pH condition that may exist and could can bring into play respective action by effective assurance medicine in different people colony.
In fact, the bioavailability of the size distribution of drug microparticles and medicament is not linear variation.Although prior art has been instructed the existence of the micronization technology of prasugrel, yet its bioavailability not makes patient satisfaction, is unsuitable for clinical use.Therefore, the pharmaceutical formulations of finding the micronization prasugrel with gratifying biological utilisation be suitable for clinical use become when preclinical therapy in the urgent need to.
Summary of the invention
The problems referred to above for prasugrel and salt existence thereof, the inventor is through long-term conscientious research, find that prasugrel and salt compound grain diameter thereof not are directly proportional little to its pharmacokinetics effect, superfine communication technique is applied in the preparation of prasugrel and salt compound thereof, obtain micronization prasugrel in specified particle diameter and the particle of salt compound thereof, can significantly improve the solvability in its water, produced beyond thought effect, greatly improve bioavailability, thereby completed the present invention.
The object of the present invention is to provide the compound of a kind of micronized prasugrel and salt thereof, its particle diameter is 3-10 μ m.Prasugrel molecular formula C
20h
20fNO
3s, molecular weight 373.44, structural formula is:
Described prasugrel and salt thereof comprise prasugrel, hydrochloric acid prasugrel, prasugrel hydrobromide, fumaric acid prasugrel, Phenylsulfonic acid prasugrel, prasugrel hydrobromide acetic acid compound, hydrochloric acid prasugrel acetic acid compound, fumaric acid prasugrel acetic acid compound, Phenylsulfonic acid prasugrel acetic acid compound.
The present invention also provides the method for the compound of a kind of micronization prasugrel and salt thereof, is about to prasugrel and salt thereof and carries out precomminution, and making particle diameter is 70-150 μ m particle, then adopts superfine communication technique to carry out micronization, and making particle diameter is 3-10 μ m fine powder.
As the present invention's one preferred embodiment, precomminution adopts the conventional crushing technology in this area to carry out, and described technology comprises, but be not limited to grind, push, collide, cut, shredding unit used includes, but are not limited to mortar, ball mill, fluid energy mill, preferably adopts the fluid energy mill of impacting technology.
As the present invention's one preferred embodiment, superfine communication technique is selected from mechanical disintegration, vibrant pulverization, comminution by gas stream, ultrasonication, high pressure grinding, preferably airflow pulverization.The superfine communication technique equipment therefor is selected from QWJ-5 air-flow vortex pulverizer, QWJ-15 air-flow vortex pulverizer, CWM-80 super vortex mill, CWM-120 super vortex mill, CWJ-30 supper micron mill, CWJ-45 supper micron mill, preferably CWJ-30 type supper micron mill.
Preferred, the concrete operation step that described airflow pulverization adopts is as follows: by precomminution, be that coarse grained prasugrel and salt thereof and the rare gas element after lyophilize inject supper micron mill jointly, adopt high velocity air to be pulverized, preferably, rare gas element after lyophilize, preferred air or nitrogen, temperature is 0-15 ℃, preferably 5 ℃-10 ℃, water content≤1%, during the air Injection supper micron mill, pressure is 0.8-1.5MPa, preferred 1.1-1.2MPa, the operating pressure of supper micron mill is 0.8-1.5MPa, preferred 1.1-1.2MPa, the internal work temperature is 0-8 ℃, preferably 2 ℃-6 ℃, grinding time is 30-200min, preferred 50-150min.
Another object of the present invention is to provide a kind of pharmaceutical composition that contains micronized prasugrel and salt thereof, and it can be tablet, capsule and granule.This pharmaceutical composition comprises prasugrel and salt and suitable auxiliary material, and wherein prasugrel and salt thereof account for the 0.1%-10% of pharmaceutical composition gross weight.
The auxiliary material of the pharmaceutical composition of prasugrel of the present invention and salt thereof, include but not limited to disintegrating agent, weighting agent, tackiness agent, wetting agent, lubricant, sweeting agent etc., wherein disintegrating agent is selected from one or more in carboxymethylstach sodium, croscarmellose sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose; Weighting agent is selected from one or more in lactose, Microcrystalline Cellulose, starch, sucrose, pregelatinized Starch, dicalcium phosphate dihydrate, N.F,USP MANNITOL, sorbyl alcohol; Tackiness agent is selected from one or more in hypromellose, PVP K30, Xylo-Mucine, starch slurry; Wetting agent is selected from the second alcohol and water; Lubricant is selected from one or more in Magnesium Stearate, silicon-dioxide, talcum powder, sodium lauryl sulphate, sodium stearyl fumarate, PEG6000; Sweeting agent is selected from one or more in aspartame, Steviosin, Sucralose, soluble saccharin.
The pharmaceutical composition of prasugrel of the present invention and salt thereof, its preparation method comprises the steps:
(1) be that the prasugrel of 3-10 μ m and salt thereof and disintegrating agent, weighting agent philosophy are crossed 100 mesh sieves by micronized particle diameter, then mix;
(2) add binder solution or wetting agent in the supplementary material powder mixed, prepare softwood, cross 20-30 mesh sieve wet granular processed, 50-70 ℃ of forced air drying 30-90 minute;
(3) dry particle is crossed the whole grain of 18 mesh sieves, adds always mixed 5-15 minute of lubricant, mixes;
(4) compressing tablet, filled capsules or pack, obtain.
The present invention adopts superfine communication technique to prepare prasugrel that particle diameter is 3-10 μ m and the compound of salt thereof, has improved the water-soluble of prasugrel and salt thereof, has improved bioavailability, has increased the clinical efficacy of pharmaceutical preparation.
The accompanying drawing explanation
Fig. 1 has illustrated the prasugrel salt extremely with specified particle diameter, makes supersaturated solution, by detection level, calculates prasugrel and the solubleness of salt in water thereof.
embodiment
Provide as follows the specific embodiment of the present invention, be to be understood that the present invention is not limited to these concrete embodiments, those skilled in the art can not deviate under the spirit and scope of the present invention, can carry out various modifications and change to the present invention, but such improvement is considered to all be included in the scope of the application's claims.
The micronization of embodiment 1 prasugrel
(1) prasugrel is adopted the fluid energy mill of impacting technology carry out precomminution, making particle diameter is 150 μ m particles;
(2) adopt CWJ-30 type supper micron mill to carry out micronizing to above-mentioned coarse particles, be ground into 3-10 μ m fine powder;
Pulverization conditions: the air themperature after lyophilize is 6 ℃, water content 0.5%, and while injecting supper micron mill, pressure is 0.8MPa, and the operating pressure of supper micron mill is 0.8MPa, and the internal work temperature is 6 ℃, and grinding time is 50min.
The micronization of embodiment 2 hydrochloric acid prasugrels
(1) adopt the fluid energy mill of impacting technology to carry out precomminution the hydrochloric acid prasugrel, making particle diameter is 250 μ m particles;
(2) adopt CWJ-30 type supper micron mill to carry out micronizing to above-mentioned coarse particles, be ground into 3-10 μ m fine powder;
Pulverization conditions: the air themperature after lyophilize is 10 ℃, water content 0.4%, and while injecting supper micron mill, pressure is 1.2MPa, and the operating pressure of supper micron mill is 1.1MPa, and the internal work temperature is 2 ℃, and grinding time is 100min.
The micronization of embodiment 3 prasugrel hydrobromides
(1) prasugrel hydrobromide is adopted the fluid energy mill of impacting technology carry out precomminution, making particle diameter is 200 μ m particles;
(2) adopt CWJ-30 type supper micron mill to carry out micronizing to above-mentioned coarse particles, be ground into 3-10 μ m fine powder;
Pulverization conditions: the air themperature after lyophilize is 8 ℃, water content 0.7%, and while injecting supper micron mill, pressure is 1.5MPa, and the operating pressure of supper micron mill is 1.2MPa, and the internal work temperature is 4 ℃, and grinding time is 150min.
The micronization of embodiment 4 prasugrel hydrobromide acetic acid compounds
(1) adopt the fluid energy mill of impacting technology to carry out precomminution prasugrel hydrobromide acetic acid compound, making particle diameter is 200 μ m particles;
(2) adopt CWJ-30 type supper micron mill to carry out micronizing to above-mentioned coarse particles, be ground into 3-10 μ m fine powder;
Pulverization conditions: the air themperature after lyophilize is 8 ℃, water content 0.6%, and while injecting supper micron mill, pressure is 1.0MPa, and the operating pressure of supper micron mill is 1.1MPa, and the internal work temperature is 5 ℃, and grinding time is 130min.
The preparation of embodiment 5 prasugrel sheets
(1) be that the prasugrel 10g of 3-10 μ m and croscarmellose sodium 20g, N.F,USP MANNITOL 50g, Microcrystalline Cellulose 120g cross respectively 100 mesh sieves by micronized particle diameter, then mix;
(2) in the supplementary material powder mixed, add 2% hypromellose 50% ethanolic soln to prepare softwood, cross 20 mesh sieve wet granular processed, 50 ℃ of forced air dryings 90 minutes;
(3) dry particle is crossed the whole grain of 18 mesh sieves, adds lubricant always mixed 5 minutes, mixes;
(4) compressing tablet, obtain.
The preparation of embodiment 6 hydrochloric acid prasugrel sheets
(1) be that the hydrochloric acid prasugrel 5g of 3-10 μ m and croscarmellose sodium 8g, N.F,USP MANNITOL 30g, Microcrystalline Cellulose 57g cross respectively 100 mesh sieves by micronized particle diameter, then mix;
(2) in the supplementary material powder mixed, add 20% ethanolic soln of 5% PVP K30 to prepare softwood, cross 30 mesh sieve wet granular processed, 70 ℃ of forced air dryings 30 minutes;
(3) dry particle is crossed the whole grain of 18 mesh sieves, adds lubricant always mixed 15 minutes, mixes;
(4) compressing tablet, obtain.
The preparation of embodiment 7 prasugrel hydrobromide particles
(1) be that the prasugrel hydrobromide 5g of 3-10 μ m and carboxymethylstach sodium 40g, sucrose 700g, N.F,USP MANNITOL 150g, Microcrystalline Cellulose 80g, aspartame 30g cross respectively 100 mesh sieves by micronized particle diameter, then mix;
(2) in the supplementary material powder mixed, add 2% hypromellose 50% ethanolic soln to prepare softwood, cross 20 mesh sieve wet granular processed, 60 ℃ of forced air dryings 70 minutes;
(3) dry particle is crossed the whole grain of 18 mesh sieves, adds lubricant always mixed 10 minutes, mixes;
(4) pack, obtain.
The preparation of embodiment 8 prasugrel hydrobromide acetic acid compound capsules
(1) be that the prasugrel hydrobromide acetic acid compound 10g of 3-10 μ m and croscarmellose sodium 30g, N.F,USP MANNITOL 60g, Microcrystalline Cellulose 100g cross respectively 100 mesh sieves by micronized particle diameter, then mix;
(2) in the supplementary material powder mixed, add 50% ethanolic soln of 5% PVP K30 to prepare softwood, cross 24 mesh sieve wet granular processed, 60 ℃ of forced air dryings 60 minutes;
(3) dry particle is crossed the whole grain of 18 mesh sieves, adds lubricant always mixed 8 minutes, mixes;
(4) filled capsules, obtain.
Embodiment 9 solubility tests
Prasugrel and salt thereof prepared by embodiment 1-4 are soluble in water, make supersaturated solution, by detection level, calculate prasugrel and the solubleness of salt in water thereof, and and without micronized raw material, contrasted, result is as follows:
| Material | Without micronization | After micronization |
| Prasugrel | 0.71μg/ml | 1.33μg/ml |
| The hydrochloric acid prasugrel | 0.78μg/ml | 1.45μg/ml |
| Prasugrel hydrobromide | 0.65μg/ml | 1.29μg/ml |
| Prasugrel hydrobromide acetic acid compound | 0.82μg/ml | 1.63μg/ml |
Comparative Examples 1 adopts prescription and the technique identical with embodiment 5, and difference is to select without micronized prasugrel raw material.
Comparative Examples 2 adopts prescription and the technique identical with embodiment 6, and difference is to select without micronized hydrochloric acid prasugrel raw material.
Comparative Examples 3 adopts prescription and the technique identical with embodiment 7, and difference is to select without micronized prasugrel hydrobromide raw material.
Comparative Examples 4 adopts prescription and the technique identical with embodiment 8, and difference is to select without micronized prasugrel hydrobromide acetic acid compound raw material.
Embodiment 10 dissolution in vitro tests
Prasugrel prepared by embodiment 5-8 and Comparative Examples 1-4 and the preparation of salt thereof carry out the dissolution in vitro detection, concrete grammar is: get this product, according to dissolution method (Chinese Pharmacopoeia version appendix X C the second method in 2010), the pH4.0 Citric Acid phosphate buffered saline buffer 900ml of take is solvent, rotating speed is that per minute 75 turns, operation in accordance with the law, sampling in the time of 45 minutes, adopt high-efficient liquid phase technique to be detected, result is as follows:
| Sample | Dissolution rate (%) |
| Embodiment 5 | 95.6 |
| Embodiment 6 | 98.8 |
| Embodiment 7 | 93.2 |
| Embodiment 8 | 99.7 |
| Comparative Examples 1 | 66.7 |
| Comparative Examples 2 | 71.3 |
| Comparative Examples 3 | 60.5 |
| Comparative Examples 4 | 76.4 |
Conclusion: can be found out by above test-results, the sample dissolution rate of embodiment 5-8 prepared by the micronized prasugrel of process and salt thereof is apparently higher than the sample prepared without micronized Comparative Examples 1-4, illustrate that prasugrel and salt thereof are after micronizing reduces particle diameter, the dissolution rate of related preparations improves greatly, and in body, bioavailability also improves thereupon.
The prasugrel of embodiment 11 different-grain diameters and the dissolubility test of salt thereof
According to the preparation technology of embodiment 1-4, the prasugrel that preparation has a specified particle diameter is salt extremely, makes supersaturated solution, by detection level, calculates prasugrel and the solubleness of salt in water thereof, and result is as follows:
| Product | Particle diameter<3 μ m | Particle diameter 3-10 μ m | Particle diameter 10-25 μ m | Particle diameter>25 μ m |
| Prasugrel | 1.44μg/ml | 1.33μg/ml | 1.04μg/ml | 0.82μg/ml |
| The hydrochloric acid prasugrel | 1.57μg/ml | 1.45μg/ml | 1.07μg/ml | 0.86μg/ml |
| Prasugrel hydrobromide | 1.43μg/ml | 1.29μg/ml | 1.00μg/ml | 0.79μg/ml |
| Prasugrel hydrobromide acetic acid compound | 1.71μg/ml | 1.63μg/ml | 1.12μg/ml | 0.91μg/ml |
According to above data, the prasugrel of different-grain diameter and the solubility curve of salt thereof are illustrated in fig. 1 shown below.Conclusion: from above testing data and curve, the solubleness of prasugrel and salt thereof reduces along with the increase of particle diameter.
The prasugrel of embodiment 12 different-grain diameters and the test of the bioavailability of salt thereof
According to the preparation technology of embodiment 5-8, adopt respectively the prasugrel of specified particle diameter and salt thereof to prepare corresponding preparation, then oral rear by detecting Plasma Concentration, judge its bioavailability, result:
Conclusion: known by above-mentioned data, preparation bioavailability the best prepared by the prasugrel of particle diameter 3-10 μ m and salt thereof, be the prasugrel of particle diameter<3 μ m and preparation bioavailability prepared by salt thereof and then, and be much higher than particle diameter and be greater than the prasugrel of 10 μ m and preparation prepared by salt thereof; So select prasugrel and the salt thereof of particle diameter 3-10 μ m both to guarantee bioavailability, make again production technique feasible, absolutely proved benefit of the present invention and innovation.
Claims (7)
1. the compound of a micronized prasugrel and salt thereof, is characterized in that the particle diameter after prasugrel and salt micronization thereof is 3-10 μ m, prasugrel molecular formula C
20h
20fNO
3s, molecular weight 373.44, structural formula is:
2. the compound of micronized prasugrel according to claim 1 and salt thereof, is characterized in that described prasugrel and salt thereof comprise prasugrel, hydrochloric acid prasugrel, prasugrel hydrobromide, fumaric acid prasugrel, Phenylsulfonic acid prasugrel, prasugrel hydrobromide acetic acid compound, hydrochloric acid prasugrel acetic acid compound, fumaric acid prasugrel acetic acid compound, Phenylsulfonic acid prasugrel acetic acid compound, naphthalene disulfonic acid prasugrel and acetic acid compound thereof.
3. the compound of micronized prasugrel according to claim 1 and salt thereof, it is characterized in that prasugrel and salt thereof are carried out to precomminution, making particle diameter is 70-150 μ m particle, then adopts superfine communication technique to carry out micronization, and making particle diameter is 3-10 μ m fine powder.
4. the compound of micronized prasugrel according to claim 3 and salt thereof, it is characterized in that precomminution adopts the conventional crushing technology in this area to carry out, described technology comprises, but be not limited to grind, push, collide, cut, shredding unit used comprises, but be not limited to mortar, ball mill, fluid energy mill, preferably adopt the fluid energy mill of impacting technology.
5. the compound of micronized prasugrel according to claim 3 and salt thereof, is characterized in that superfine communication technique is selected from mechanical disintegration, vibrant pulverization, comminution by gas stream, ultrasonication, high pressure grinding, preferably airflow pulverization.
6. a pharmaceutical composition that contains micronized prasugrel and salt thereof, is characterized in that can being tablet, capsule and granule.
7. pharmaceutical composition according to claim 6, is characterized in that this pharmaceutical composition comprises prasugrel and salt and suitable auxiliary material, and wherein prasugrel and salt thereof account for the 0.1%-10% of gross weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310388714.XA CN103467484B (en) | 2013-08-30 | 2013-08-30 | Compound and medicine composition containing micronized prasugrel and salts of prasugrel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310388714.XA CN103467484B (en) | 2013-08-30 | 2013-08-30 | Compound and medicine composition containing micronized prasugrel and salts of prasugrel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103467484A true CN103467484A (en) | 2013-12-25 |
| CN103467484B CN103467484B (en) | 2014-11-19 |
Family
ID=49792556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310388714.XA Expired - Fee Related CN103467484B (en) | 2013-08-30 | 2013-08-30 | Compound and medicine composition containing micronized prasugrel and salts of prasugrel |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103467484B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN106913549A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of prasugrel tablets and preparation method thereof |
| 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 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090281136A1 (en) * | 2008-05-08 | 2009-11-12 | Sandeep Mhetre | Prasugrel pharmaceutical formulations |
| CN102232949A (en) * | 2010-04-27 | 2011-11-09 | 孙远 | Drug dissolution increasing composition and preparation method thereof |
| CN102675338A (en) * | 2011-03-11 | 2012-09-19 | 上海现代制药股份有限公司 | Micronization prasugrel and medicinal composition of prasugrel |
-
2013
- 2013-08-30 CN CN201310388714.XA patent/CN103467484B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090281136A1 (en) * | 2008-05-08 | 2009-11-12 | Sandeep Mhetre | Prasugrel pharmaceutical formulations |
| CN102232949A (en) * | 2010-04-27 | 2011-11-09 | 孙远 | Drug dissolution increasing composition and preparation method thereof |
| CN102675338A (en) * | 2011-03-11 | 2012-09-19 | 上海现代制药股份有限公司 | Micronization prasugrel and medicinal composition of prasugrel |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| CN106913549A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of prasugrel tablets and preparation method thereof |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103467484B (en) | 2014-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102770127B (en) | Abuse-resistant formulations | |
| TWI235658B (en) | beta-carboline drug products | |
| CN104083328B (en) | Pharmaceutical Compositions Comprising 2-Oxo-1-Pyrrolidine Derivatives | |
| CN101862297A (en) | Water-insoluble medicine sustained-release pellet, sustained-release orally disintegrating tablet thereof and preparation method thereof | |
| CN104721156B (en) | Rivaroxaban-containing tablet | |
| CN101390846B (en) | Amoxicillin capsule and production method thereof | |
| CN104398481A (en) | Bilastine orally disintegrating tablet and preparing method thereof | |
| CN103467484B (en) | Compound and medicine composition containing micronized prasugrel and salts of prasugrel | |
| WO2015081703A1 (en) | Solid dispersion containing desmodium styracifolium (osb.) merr. flavonoids, method of preparing same, and use thereof | |
| Obaidat et al. | Development and evaluation of fast-dissolving tablets of meloxicam-β-cyclodextrin complex prepared by direct compression | |
| CN104721207B (en) | A kind of pharmaceutical composition | |
| CN101284011B (en) | Oleanolic acid orally disintegrating tablet and preparation method thereof | |
| CN101568329A (en) | Dry granulated pharmaceutical compositions and methods for producing same | |
| CN103393612B (en) | Preparation method for enalapril maleate orally disintegrating tablets | |
| CN103610674B (en) | Solid preparation containing micronized prasugrel | |
| CN103284953B (en) | Bicyclol solid preparation and preparation method thereof | |
| CN104257611B (en) | Pharmaceutical composition containing micronized fexofenadine hydrochloride | |
| US20100034887A1 (en) | Bursting Pellets | |
| CN105106250A (en) | Mythic Fungus total triterpene composition and preparation methods thereof | |
| CN109718211A (en) | A kind of Fructus Forsythiae aglycone preparation | |
| CN111450163B (en) | Coptis pharmaceutical composition and application thereof | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof | |
| CN105853385A (en) | Ticagrelor oral-disintegrating sustained release tablet and preparation method thereof | |
| CN101129370A (en) | Rimonabant or its salt dispersion patch capable of using in medicine and method of producing the same | |
| Tat et al. | A REVIEW ON UTILIZATION OF NATURAL SUPERDISINTEGRANT IN THE ADVANCEMENT OF ORALLY DISPERSIBLE TABLET |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141119 Termination date: 20160830 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |