EP2451816A1 - Crystalline form of prasugrel hydrobromide, preparation and application thereof - Google Patents
Crystalline form of prasugrel hydrobromide, preparation and application thereofInfo
- Publication number
- EP2451816A1 EP2451816A1 EP10796816.6A EP10796816A EP2451816A1 EP 2451816 A1 EP2451816 A1 EP 2451816A1 EP 10796816 A EP10796816 A EP 10796816A EP 2451816 A1 EP2451816 A1 EP 2451816A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- prasugrel
- prasugrel hydrobromide
- crystalline form
- hydrobromide
- crystalline
- 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.)
- Withdrawn
Links
Classifications
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Definitions
- the present invention relates to crystalline form of prasugrel hydrobromide and process for the preparation thereof.
- the present invention also relates to a pharmaceutical composition comprising crystalline form of prasugrel hydrobromide.
- Prasugrel is a P2Y12 (P2T) antagonist which has been filed for regulatory approval in the U.S. and approved in Europe for the secondary prevention of thrombotic cardiovascular complications.
- Prasugrel hydrochloride is chemically described as 5-[2- cyclopropyl-1 -(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate and is represented by the structural formula below;
- Prasugrel hydrobromide is chemically described as 2-acetoxy-5-(.alpha.- cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
- hydrobromide and can be represented by structural formula:
- HBr U.S. Patent No. 5,288,726 describes tetrahydrothienopyridine derivatives, including prasugrel and their pharmaceutically acceptable salts, a pharmaceutical composition and method of treatment.
- U.S. Patent No. 6,693,115 discloses crystal A, crystal Bl and crystal B2 of prasugrel hydrochloride and processes for the preparation thereof.
- European Patent No. 2003136 describes crystal A, crystal Bl and crystal B2 of prasugrel hydrochloride and processes for the preparation thereof.
- the present invention provides crystalline form of prasugrel hydrobromide and a process for the preparation thereof.
- the process of the present invention is simple, eco friendly, robust, and well suited on commercial scale.
- the present invention relates to prasugrel hydrobromide and a process for the preparation thereof. More particularly, the present invention relates to a crystalline form of prasugrel hydrobromide.
- the present invention provides a crystalline form of prasugrel hydrobromide characterized by an X- ray powder diffraction pattern with characteristic peaks at about 7.06 , 8.31, 10.08, 11.46, 12.19, 12.82, 13.73, 14.17, 15.8, 16.7, 16.98, 17.23, 17.73, 18.36, 18.70, 21.60, 23.42, 23.69, 24.21, 24.39, 24.9, 25.14, 25.82, 26.50, 27.0, 29.89, 30.31 and 37.2 ⁇ 0.2 degrees two-theta, which is substantially in accordance with Fig. 1.
- the present invention provides the crystalline form of prasugrel hydrobromide characterized by differential scanning calorimetry with an endotherm curve at about 138.25°C with an onset at about 128.29 0 C and an endset at about 146.34°C, which is substantially in accordance with Fig. 2.
- the present invention provides crystalline form of prasugrel hydrobromide further characterized by an infrared absorption spectrum, which is substantially in accordance with Fig. 3.
- the present invention provides the crystalline form of prasugrel hydrobromide further characterized by an mass spectrum, which is substantially in accordance with Fig. 4.
- the present invention provides a process for preparing crystalline form of prasugrel hydrobromide comprising:
- the present invention provides a process for conversion of prasugrel hydrobromide into prasugrel hydrochloride comprising:
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising crystalline form of prasugrel hydrobromide and at least a pharmaceutically acceptable carrier.
- Fig. 1 X-ray powder diffraction pattern of prasugrel hydrobromide crystalline form, as prepared by Example 1.
- Fig. 2 Differential scanning calorimetry of prasugrel hydrobromide crystalline form, as prepared by Example 1.
- Fig. 3 infrared absorption spectrum of prasugrel hydrobromide crystalline form, as
- Fig. 4 MASS spectrum of prasugrel hydrobromide, as prepared by Example 1. DETAILED DESCRIPTION OF THE INVENTION
- the present invention relates to prasugrel hydrobromide and a process for the preparation thereof. More particularly, the present invention relates to a crystalline form of prasugrel hydrobromide.
- Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes. Polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties. Therefore, a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as different solubility profiles, different melting point temperatures and/or different x-ray diffraction peaks. The solubility of each polymorph may vary, which makes identifying the existence of pharmaceutical polymorphs essential for providing pharmaceuticals with predictable solubility profiles. It is desirable to investigate all solid state forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in a laboratory, by methods, known in the art, which include X-ray diffraction spectroscopy and infrared spectrometry.
- polymorphic forms of the same drug substance or active pharmaceutical ingredient can be administered by itself or formulated as a drug product (also known as the final or finished dosage form), and are well known in the
- the present invention provides the crystalline form of prasugrel HBr and a process for its preparation, which is simple, ecofriendly, inexpensive, reproducible, robust and well suited on commercial scale.
- the present invention provides a crystalline form of prasugrel hydrobromide characterized by an X- ray powder diffraction pattern with characteristic peaks at about 7.06, 8.31, 10.08, 11.46, 12.19, 12.82, 13.73, 14.17, 15.8, 16.7, 16.98, 17.23, 17.73, 18.36, 18.70, 21.60, 23.42, 23.69, 24.21, 24.39, 24.9, 25.14, 25.82, 26.50, 27.0, 29.89, 30.31 and 37.2 ⁇ 0.2 degrees two-theta, which is substantially in accordance with Fig. 1.
- the present invention further provides the crystalline form of prasugrel hydrobromide as characterized by differential scanning calorimetry with an endotherm curve at about 138.25°C, with an onset at about 128.29°C and an endset at about 146.34°C, which is substantially in accordance with Fig. 2.
- the present invention provides the crystalline form of prasugrel hydrobromide characterized by an infrared absorption spectrum, which is substantially in accordance with Fig. 3.
- the present invention provides the crystalline form of prasugrel hydrobromide further characterized by an mass spectrum, which is substantially in accordance with Fig. 4.
- the present invention provides a process for preparing crystalline form of prasugrel hydrobromide comprising:
- the solution of prasugrel and hydrobromic acid can be obtained by dissolving prasugrel and hydrobromic acid, either separately or together in a solvent or mixture of solvents or their aqueous mixtures, either by agitation at room temperature or at elevated temperatures.
- a solvent is any liquid substance capable of dissolving prasugrel and hydrobromic acid.
- a mixture of solvents refers to a composition comprising of more than one solvent.
- the solvents that can be used include, but are not limited to water, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, and tertiary butyl alcohol and the like; ketonic solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone, 2-butanone and the like; nitrile solvents such as acetonitrile, propionitrile and the like; or mixtures thereof or their aqueous mixtures in various proportions without limitation.
- acetone or acetonitrile or their aqueous mixtures Preferably, acetone or acetonitrile or their aqueous mixtures.
- the volume of the solvent used to solubilize prasugrel and hydrobromic acid can range from about 2 volumes to about 20 volumes of the weight of the prasugrel free base taken, preferably from about 15 volumes to about 18 volumes.
- the molar ratio of hydrobromic acid to prasugrel is preferably about 1 : 1 to about 1.2:1.
- hydrobromic acid used herein can be of any percentage and in any form, either as a gas or in solution.
- the temperature for obtaining a clear and homogenous solution can range from about 25°C to about 75°C or the boiling point of the solvent/s used, preferably from about 25°C to about 40°C.
- the solution obtained is optionally filtered through celite or diatomaceous earth to separate the extraneous matter present or formed in the solution by using conventional filtration techniques known in the art.
- the solid prasugrel hydrobromide is then precipitated out from the solution by maintaining the solution at room temperature or below with or without stirring or by addition of an anti-solvent to the solution.
- the anti-solvent is a solvent which is capable of inducing precipitation of the solid prasugrel hydrobromide from the solution.
- the solid prasugrel hydrobromide is precipitated out from the solution by stirring at about room temperature for a period of about 1 hour to about 3 hours.
- Recovery of crystalline form of prasugrel hydrobromide obtained by the above process can be performed by any conventional method, known in the art, such as filtration, decantation and centrifugation.
- recovery comprises filtering, washing, and drying the solid. Washing is usually done with the same solvent used in the reaction.
- the crystalline form of prasugrel hydrobromide obtained by the above process may be further dried in, for example, a vacuum tray dryer, a rotocon vacuum dryer, a vacuum paddle dryer or a pilot plant rotavapor, to further lower residual solvents.
- a vacuum tray dryer When implemented, the preferred instrument is a vacuum tray dryer.
- the temperature for drying can range from about 25°C to about 6O 0 C, preferably from about 50°C to about 60 0 C under vacuum.
- the drying can be carried out for any desired time, till a constant weight is obtained and time periods can range from about 1 hour to about 50 hours, preferably from about 40 hours to about 50 hours.
- the prasugrel freebase used as starting material in the processes described herein above may be of an indefinite morphology, i.e. crystalline or crude or mixtures thereof resulting from synthetic process known in the art.
- these processes are disclosed in U.S. Patent Nos. 5288726 and 6693115, both of which are incorporated herein in their entirety by reference.
- the X-ray source is operated at 45 kV and 4OmA. Spectra are recorded in the 2 ⁇ range of 2-50°, a step size 0.0167° with a "time-per-step" optimized to 1000 seconds.
- DSC Differential scanning calorimetry
- FTIR method IR is measured by using instrument Perkin Elmer by KBr mode.
- the present invention provides substantially pure crystalline form of prasugrel hydrobromide having less than 20% of amorphous form of prasugrel hydrobromide as determined by x-ray powder diffraction. More preferably less than 10% of amorphous form of prasugrel hydrobromide as determined by x-ray powder diffraction. Even more preferably less than about 5% of amorphous form of prasugrel hydrobromide as determined by x-ray powder diffraction and most preferably less than 1 % of amorphous form of prasugrel hydrobromide as determined by x-ray powder diffraction
- the x-ray powder diffraction (PXRD) pattern of the pure crystalline form of prasugrel hydrobromide is substantially in accordance with Fig.l.
- the present invention provides the crystalline prasugrel hydrobromide having a purity, as measured by high performance liquid chromatography (HPLC), of at least about 98%, more preferably, at least about 99% and most preferably at least about 99.5%.
- HPLC high performance liquid chromatography
- the chemical purity of the prasugrel hydrobromide is about 99% or more, more preferably about 99.5% or more, more preferably about 99.8% or more, more preferably about 99.9% or more, as measured by HPLC.
- the present invention encompasses prasugrel hydrobromide having less than about 0.20% of any single impurity as measured by HPLC.
- the prasugrel or a pharmaceutically acceptable salt thereof has less than about 0.15% of any single chemical impurity as measured by HPLC.
- the prasugrel HBr is converted into a hydrochloride salt of prasugrel by general methods known in the art.
- the salt transformation may be by neutralizing the HBr salt of prasugrel by using a base to give prasugrel freebase and then followed by the reaction of freebase with hydrochloric acid to give the hydrochloride salt of prasugrel which is herein described in the example 2.
- the present invention provides a process for the conversion of prasugrel hydrobromide into prasugrel hydrochloride comprising:
- the prasugrel hydrobromide is suspended in a solvent.
- ethyl acetate is used as a solvent.
- a base is then added to the suspension to obtain a clear solution.
- the base is selected from an organic base or inorganic base.
- the organic base may be selected from trimethylamine, triethylamine, tripropylamine.
- the inorganic base may be selected from carbonate or a hydroxide of an alkaline metal or an alkaline earth metal such as sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide.
- triethylamine is used as a base.
- the hydrochloric acid is then added to the clear solution and the obtained prasugrel hydrochloride is recovered by standard techniques.
- the reaction mixture is washed with water and the organic layer containing the product is separated.
- the organic solvent is distilled out and one or more solvents like alcohol is added to the residue and removed.
- the solid obtained is dissolved in a solvent like acetone to obtain a clear solution.
- the hydrochloric acid is then added to the clear solution and the obtained prasugrel hydrochloride is recovered by standard techniques.
- Prasugrel hydrobromide obtained by the process described above has residual organic solvents or organic volatile impurities comprises less than the amount recommended for pharmaceutical products, as set forth for example in ICH guidelines and U.S. pharmacopoeia; less than about 600ppm of dichloromethane, less than about 5000ppm of ethanol, acetone, ethyl acetate, isopropyl alcohol, less than about 890 ppm of toluene and less than about 290ppm of n-hexane.
- D 90 particle size of the unformulated crystalline prasugrel hydrobromide salt obtained by the process of present invention is used as starting material in preparing a pharmaceutical composition generally is less than 400 microns preferably less than about 200 microns, more preferably less than 150 microns, still more preferably less than about 50 microns and still more preferably less than about 15 microns.
- Any milling, grinding micronizing or other particle size reduction method known in the art can be used to bring the crystalline prasugrel hydrobromide into any desired particle size' range as set forth above.
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising crystalline form of prasugrel hydrobromide and at least a pharmaceutically acceptable carrier.
- Such pharmaceutical compositions may be administered to a mammalian patient in any dosage form, e.g., liquid, powder, elixir, injectable solution, etc.
- Dosage forms may be adapted for administration to the patient by oral, buccal, parenteral, ophthalmic, rectal and transdermal routes.
- Oral dosage forms include, but are not limited to, tablets, pills, capsules, troches, sachets, suspensions, powders, lozenges, elixirs and the like.
- the prasugrel or its pharmaceutically acceptable salts obtained by the process disclosed herein also may be administered as suppositories, ophthalmic ointments and suspensions, and parenteral suspensions, which are administered by other routes.
- the most preferred route of administration of the prasugrel or its pharmaceutically acceptable salts is oral.
- the dosage forms may contain the prasugrel or its pharmaceutically acceptable salts as part of a composition.
- the pharmaceutical compositions may further contain one or more pharmaceutically acceptable excipients.
- Capsule dosages will contain the prasugrel or its pharmaceutically acceptable salts which may be coated with gelatin. Tablets and powders may also be coated with an enteric coating.
- the enteric-coated powder forms may have coatings comprising phthalic acid cellulose acetate, hydroxypropylmethyl cellulose phthalate, polyvinyl alcohol phthalate, carboxymethylethylcellulose, a copolymer of styrene and maleic acid, a copolymer of methacrylic acid and methyl methacrylate, and like materials, and if desired, they may be employed with suitable plasticizers and/or extending agents.
- a coated tablet may have a coating on the surface of the tablet or may be a tablet comprising a powder or granules with an enteric-coating.
- compositions of the present invention may contain diluents such as cellulose-derived materials like powdered cellulose, microcrystalline cellulose, microfine cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose salts and other substituted and unsubstituted celluloses; starch; pregelatinized starch; inorganic diluents such calcium carbonate and calcium diphosphate and other diluents known to one of ordinary skill in the art.
- diluents such as cellulose-derived materials like powdered cellulose, microcrystalline cellulose, microfine cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose salts and other substituted and unsubstituted celluloses
- starch pregelatinized starch
- Suitable diluents include waxes, sugars (e.g. lactose) and sugar alcohols like mannitol and sorbitol, acrylate polymers and copolymers, as well as pectin, dextrin and gelatin.
- excipients contemplated by the present invention include binders, such as acacia gum, pregelatinized starch, sodium alginate, glucose and other binders used in wet and dry granulation and direct compression tableting processes; disintegrants such as sodium starch glycolate, crospovidone, low-substituted hydroxypropyl cellulose and others; lubricants like magnesium and calcium stearate and sodium stearyl hydrobromide; flavorings; sweeteners; preservatives; pharmaceutically acceptable dyes and glidants such as silicon dioxide.
- binders such as acacia gum, pregelatinized starch, sodium alginate, glucose and other binders used in wet and dry granulation and direct compression tableting processes
- disintegrants such as sodium starch glycolate, crospovidone, low-substituted hydroxypropyl cellulose and others
- lubricants like magnesium and calcium stearate and sodium stearyl hydrobromide
- flavorings sweet
- the process for the preparation of crystalline prasugrel hydrobromide of the present invention is simple, eco-friendly and easily scaleable.
- Target compound has an X- ray powder diffraction (XRD) pattern with characteristic peaks at about 7.06, 8.31, 10.08, 1 1.46, 12.19, 12.82, 13.73, 14.17, 15.8, 16.7, 16.98,
- DSC Differential scanning calorimetry
- the solid obtained was dried at about 55°C under vacuum over about 12 hours.
- To the solid (6.5gm) obtained 97.5 ml of Acetone was charged and stirred for about 15 minutes to obtain clear solution. 1.5ml of concentrated HCl was added followed by stirring 4 hrs. Solid separated was filtered and the solid was washed with 2x10ml of acetone. The solid obtained was dried at about 55°C under vacuum for about 12 hrs to afford about 4gm to about 5.5gm of the title compound.
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1596MU2009 | 2009-07-06 | ||
PCT/IN2010/000435 WO2011004392A1 (en) | 2009-07-06 | 2010-06-25 | Crystalline form of prasugrel hydrobromide, preparation and application thereof |
Publications (2)
Publication Number | Publication Date |
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EP2451816A1 true EP2451816A1 (en) | 2012-05-16 |
EP2451816A4 EP2451816A4 (en) | 2013-02-27 |
Family
ID=43428854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP10796816A Withdrawn EP2451816A4 (en) | 2009-07-06 | 2010-06-25 | Crystalline form of prasugrel hydrobromide, preparation and application thereof |
Country Status (2)
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EP (1) | EP2451816A4 (en) |
WO (1) | WO2011004392A1 (en) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EA024980B1 (en) | 2009-02-17 | 2016-11-30 | КРКА, д.д., НОВО МЕСТО | Dosage forms comprising prasugrel base or its pharmaceutically acceptable acid addition salts and processes for their preparation |
EP2415774B1 (en) * | 2009-03-31 | 2014-07-09 | Shanghai Institute of Pharmaceutical Industry | Crystals of acetic acid solvate of prasugrel hydrobromate |
EP2360159A1 (en) * | 2010-02-11 | 2011-08-24 | Ratiopharm GmbH | Prasugrel in micronized, crystalline form and pharmaceutical compound of same |
SI2448945T1 (en) | 2010-04-08 | 2015-05-29 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of prasugrel salts |
CZ305314B6 (en) * | 2010-12-30 | 2015-07-29 | Zentiva, K.S. | Novel hydrobromide of the C 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate form known under unprotected name prasugrel and process for preparing thereof |
CN102746318A (en) * | 2011-04-20 | 2012-10-24 | 上海信谊药厂有限公司 | Method for preparation of Prasugrel hydrochloride |
CN103102356B (en) * | 2011-11-11 | 2016-01-27 | 山东新时代药业有限公司 | A kind of preparation method of prasugrel hydrobromide |
CZ2011872A3 (en) * | 2011-12-22 | 2013-07-03 | Zentiva, K.S. | Pharmaceutical formulation of prasugrel hydrobromide |
US8603537B2 (en) | 2012-04-02 | 2013-12-10 | Egis Pharmaceuticals Plc | Prasugrel containing quickly released stable oral pharmaceutical compositions |
CN103012427B (en) * | 2012-11-26 | 2015-07-08 | 天津大学 | Prasugrel hydrochloride ethanol solvate and preparation method thereof |
CN103232446B (en) * | 2013-05-17 | 2015-09-23 | 天津药物研究院 | Yi Zhong oxazolidinone derivative crystal form II and its production and use |
EP3106151A1 (en) | 2015-06-19 | 2016-12-21 | Sanovel Ilac Sanayi ve Ticaret A.S. | Pharmaceutical compositions of prasugrel hydrobromide |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN101255169A (en) | 2008-03-26 | 2008-09-03 | 山东大学 | Prasugrel salt and preparation method thereof |
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PT1728794E (en) * | 2000-07-06 | 2008-07-15 | Ube Industries | Maleate addition salt of hydropyridine derivatives |
TWI392681B (en) * | 2006-04-06 | 2013-04-11 | Daiichi Sankyo Co Ltd | Prasugrel with high purity and a method for preparing its acid addition salt |
CZ2009762A3 (en) * | 2009-11-16 | 2011-05-25 | Zentiva, K. S. | Novel salts of 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate known under unprotected name prasugrel and process of their preparation |
-
2010
- 2010-06-25 WO PCT/IN2010/000435 patent/WO2011004392A1/en active Application Filing
- 2010-06-25 EP EP10796816A patent/EP2451816A4/en not_active Withdrawn
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CN101255169A (en) | 2008-03-26 | 2008-09-03 | 山东大学 | Prasugrel salt and preparation method thereof |
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EP2451816A4 (en) | 2013-02-27 |
WO2011004392A1 (en) | 2011-01-13 |
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