Abstract: The invention relates to a novel salt of montelukast with tert-butylamine and its use in the process for the preparation of highly pure free montelukast acid and/or pharmaceutically acceptable salts thereof, in particular montelukast sodium.
Type:
Application
Filed:
October 21, 2005
Publication date:
January 1, 2009
Applicants:
INSTYTUT FARMACEUTYCZNY, ZAKLADY FARMACEUTYCZNE POLPHARMA SA
Inventors:
Osman Achmatowicz, Krzysztof Wisniewski, Jan Ramza, Wieslaw Szelejewski, Barbara Szechner
Abstract: Preparation of sulfonyl derivatives of cholecalciferol of Formula 1, wherein R1 is a protective group, preferably a t-butyl(dimethyl)silyl, and R2 is a heterocyclic group, such as a 2-thiazolyl, a 2-benzothiazolyl, a 1-phenyl-1H-tetrazo-5-yl, a 2-pyridyl, a 2-pyrimidynyl, a 1-isochinolinyl, a 1-methyl-2-imidazyl, or a 4-alkyl-1,2,4-triazo-3-yl, comprises the conversion of the hydroxyl derivative of cholecalciferol into the corresponding sulfide followed by its oxidation to the respective sulfone characterized by the use of a hydroxyl derivative of cholecalciferol as a starting material, in which the triene system is protected as a Diels-Alder adduct, and in particular as an adduct with sulfur dioxide of the Formula 2a. Novel are also the derivatives of Formula 3a and 4a, isolated in the process provided by the invention.
Type:
Application
Filed:
May 13, 2005
Publication date:
October 16, 2008
Applicant:
INSTYTUT FARMACEUTYCZNY
Inventors:
Michal Chodynski, Malgorzata Krupa, Hanna Fitak, Jerzy Winiarski, Teresa Ryznar, Bartlomiej Gorecki, Wieslaw Szelejewski, Andrzej Kutner
Abstract: A process for preparation of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl]-(1S,3S,5S)-2- azabicyclo [3.3.0] octane-3-carboxylic acid, ie. Ramipril, involves condensation of an activated derivative of 2-[N-](S)-1-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine with racemic (1R*,3R*,5R*)-2-azabicyclo[3.3.0]octane-3-carboxylic acid, and then the desired diastereoisomer (1a) is separated from the obtained diastereoisomeric mixture of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl](S)-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (1a) and 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl -alanyl]-(1R,3R,5R)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (1b) by treating it with a solvent that selectively dissolves the undesired diastereoisomer (1b) while the diastereoisomer (1a) remains undissolved.
Type:
Application
Filed:
May 12, 2005
Publication date:
September 25, 2008
Applicant:
INSTYTUT FARMACEUTYCZNY
Inventors:
Krzysztof Bankowski, Teresa Wachal, Katarzyna Sidoryk, Wieslaw Szelejewski
Abstract: A process for the preparation of a pharmaceutical-grade anhydrous calcipotriol comprising: (a) dissolving crude calcipotriol having a water content of X % by weight in a first solvent or in a mixture of two or more first solvents, said first solvent or said mixture of two or more first solvents forming an azeotropic system with water, to obtain a solution of crude calcipotriol; (b) obtaining an intermediate calcipotriol by (i) placing said solution of crude calcipotriol under a reduced pressure and evaporating, if X is greater than or equal to 1, or (ii) crystallizing, if X is lower than 1; and (c) re-dissolving said intermediate calcipotriol in a second solvent or a mixture of two or more second solvents, said second solvent being anhydrous, and crystallizing at least once to obtain pharmaceutical-grade anhydrous calcipotriol.
Type:
Application
Filed:
December 29, 2005
Publication date:
September 4, 2008
Applicant:
INSTYTUT FARMACEUTYCZNY
Inventors:
Andrzej Kutner, Michal Chodynski, Teresa Ryznar, Hanna Fitak, Jerzy Winiarski, Bartlomiej Gorecki, Agnieszka Burzynska, Wieslaw Szelejewski
Abstract: The invention relates to a process for the preparation of 13,14-dihydro-PGF2? derivatives of R or S configuration at carbon 15, represented by the general formula (I), wherein the identity of the substituents is defined in the description. Compounds of the formula (I) are valuable biologically-active substances or intermediates in the preparation thereof. The invention especially relates to the process for preparation of 13,14-dihydro-15(R)-17-substituted-18,19,20-trinor-PGF2?, i.e., latanoprost.
Type:
Application
Filed:
October 18, 2007
Publication date:
August 28, 2008
Applicant:
INSTYTUT FARMACEUTYCZNY
Inventors:
Jacek MARTYNOW, Julita SZYC, Wieslaw SZELEJEWSKI, Osman ACHMATOWICZ, Andrzej KUTNER, Krzysztof WISNIEWSKI, Jerzy WINIARSKI, Oliwia ZEGROCKA-STENDEL, Piotr GOLEBIEWSKI
Abstract: The invention provides an improved process for preparation of imatinib base and its pharmaceutically acceptable acid addition salts. The process allows for using simple starting materials, while simultaneously avoiding a laborious isolation and purification of intermediates and the final product, thereby facilitating scale-up.
Type:
Application
Filed:
December 30, 2005
Publication date:
August 14, 2008
Applicant:
INSTYTUT FARMACEUTYCZNY
Inventors:
Wojciech Szczepek, Wojciech Luniewski, Lukasz Kaczmarek, Bogdan Zagrodzki, Dorota Samson-Lazinska, Wieslaw Szelejewski, Maciej Skarzynski
Abstract: Taught herein is a solid, oral, controlled-release pharmaceutical composition of tamsulosin hydrochloride in the form of an enteric-coated tablet, wherein tamsulosin hydrochloride is homogenously dispersed within a matrix consisting of a mixture of a fatty component and a hydrophilic component, together with at least one diluent, and optionally other pharmaceutically acceptable excipients, exhibiting the following dissolution profile of tamsulosin hydrochloride, as measured in a Type II paddle apparatus in accordance with the dissolution testing method specified in the European Pharmacopoeia, i.e., at 37±0.5° C. and 100 rpm in a 0.1 N HCl buffer for 2 hours, followed by pH 7.2 buffer for the rest of the test: 10-40% dissolution during first 2 hours (in HCl), 35-70% dissolution after 3 h (in pH 7.2 buffer system), not less than 70% dissolution of the declared content after 5 h (in pH 7.2 buffer system).
Abstract: This invention relates to the methanesulfonic acid addition salts of Imatinib and to the synthesis thereof. In particular, this invention relates to the synthesis of crystalline ?-form of Imatinib methanesulfonate. Furthermore, the invention is directed to a novel acid addition salt of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-[(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]benzamide with two molecules of methanesulfonic acid and to the polymorphic forms thereof, as well as to their pharmaceutical compositions.
Type:
Application
Filed:
April 2, 2005
Publication date:
August 23, 2007
Applicant:
INSTYTUT FARMACEUTYCZNY
Inventors:
Wojciech Szczepek, Dorota Samson-Lazinska, Bogdan Zagrodzki, Magdalena Glice, Wioleta Maruszak, Kataryzna Korczak, Ryszard Modzelewski, Marta Lawecka, Lukasz Kaczmarek, Wieslaw Szelejewski, Urszula Fraczek, Piotr Cmoch
Abstract: Disclosed is a process for the preparation of 24-alkyl analogs of cholecalcyferol of Formula 1 having a (5E) or (5Z) configuration, wherein X represents a hydrogen atom, a hydroxy group or an OR1 group, where R1, R2 and R3 may be the same or different and represent groups suitable for hydroxyl protection, and R4 is a C1-6 alkyl chain or a C1-6 cykloalkyl group, optionally substituted with C1-3 alkyl groups, especially for calcipotriol. The invention also provides new intermediates and non-racemic compounds being valuable synthones for the synthesis of pharmacologically active substances.
Type:
Application
Filed:
October 8, 2004
Publication date:
June 2, 2005
Applicant:
Instytut Farmaceutyczny
Inventors:
Andrzej Kutner, Jacek Martynow, Michal Chodynski, Wieslaw Szelejewski, Hanna Fitak, Malgorzata Krupa