AR036339A1

AR036339A1 - MEDICINAL FORMULATION CONTAINING AN LTB4 ANTAGONIST

Info

Publication number: AR036339A1
Application number: ARP020102604A
Authority: AR
Inventors: Robert Becker; Bock Thomas Dr; Siglinde Moll; Rene Roscher; Ulrich Roth; Achim Sauer; Karl Weber
Original assignee: Boehringer Ingelheim Pharma
Priority date: 2001-07-14
Filing date: 2002-07-12
Publication date: 2004-09-01
Also published as: DE10206241A1; SA03230511A; CO5560535A2; PE20030255A1; DE50203521D1; ZA200309710B

Abstract

Una formulación de medicamento en forma de una tableta que contiene un antagonista de LTB4 de fórmula (1), en donde: A significa un grupo de la fórmula -O-CmH2m-O-(PHE)n- en donde m es un número entero de 2 a 6, n es 0 ó 1, PHE representa un grupo 1,4-fenileno eventualmente sustituido con uno o dos grupos alquilo C1-6; o A significa un grupo de fórmula (2); R1 significa H, OH, CN, COOR10 o CHO; R2 significa H, Br, Cl, F, CF3, CHF2, OH, HSO3-O-, alquilo C1-6, alcoxi C1-6, cicloalquilo C5-7, CONR8R9, arilo, O-arilo, CH2-arilo, CR5R6-arilo o C(CH3)2-R7; R3 significa H, alquilo C1-6, alcoxi C1-6, OH, Cl o F; R4 significa H o alquilo C1-6; R5 significa alquilo C1-4, CF3, CH2OH, COOH o COO(alquilo C1-4); R6 significa H, alquilo C1-4 o CF3; R7 significa CH2OH, COOH, COO(alquilo C1-4), CONR8R9 o CH2NR8R9; R8 significa H, alquilo C1-6, fenilo, fenil-(alquilo C1-6), COR10, COOR10, CHO, CONH2, CONHR10, SO2-(alquilo C1-6), SO2-fenilo, pudiendo estar sustituido una o dos veces el grupo fenilo con Cl, F, CF3, alquilo C1-4, OH y/o alcoxi C1-4; R9 significa H o alquilo C1-6; o R8 y R9 tomados juntos, significan un grupo alquileno C4-6; R10 significa alquilo C1-6, cicloalquilo C5-7, arilo, heteroarilo, aralquilo o heteroaril-(alquilo C1-6); representando los grupos arilo de los radicales R2 y R10 fenilo o naftilo, representando los grupos heteroarilo, pirrol, pirazol, imidazol, furanilo, tienilo, piridina o pirimidina, y pudiendo estar sustituidos en cada caso, una o varias veces, con Cl, F, CF3, alquilo C1-4, OH, HSO3-O- o alcoxi C1-4, así como sus sales por adición de ácidos farmacológicamente aceptables y glucósidos y o-sulfatos; y al menos un coadyuvante farmacológicamente aceptable, caracterizada porque la tableta contiene al menos un agente humectante. Esta formulación farmacéutica, aplicable por vía oral, libera el principio activo de fórmula (1) con relativa rapidez y por completo y, por lo tanto, conduce a una elevada biodisponibilidad de este principio activo. Además, está caracterizada por una buena manipulabilidad durante el proceso de fabricación y permite con ello la preparación técnica de modo reproducible y con calidad invariablemente elevada. Procedimiento para la preparación de las tabletas descriptas más arriba, así como su uso para la preparación de un medicamento destinado al tratamiento o la prevención de la artritis, el asma, las afecciones pulmonares obstructivas crónicas, la psoriasis, la colitis ulcerosa, la enfermedad de Alzheimer, el choque (schock), las lesiones por reperfusión/isquemia, la fibrosis quística, la arterioesclerosis y la esclerosis múltiple.A medicament formulation in the form of a tablet containing an LTB4 antagonist of formula (1), wherein: A means a group of the formula -O-CmH2m-O- (PHE) n- where m is an integer from 2 to 6, n is 0 or 1, PHE represents a 1,4-phenylene group optionally substituted with one or two C1-6 alkyl groups; or A means a group of formula (2); R1 means H, OH, CN, COOR10 or CHO; R2 means H, Br, Cl, F, CF3, CHF2, OH, HSO3-O-, C1-6 alkyl, C1-6 alkoxy, C5-7 cycloalkyl, CONR8R9, aryl, O-aryl, CH2-aryl, CR5R6- aryl or C (CH3) 2-R7; R3 means H, C1-6 alkyl, C1-6 alkoxy, OH, Cl or F; R4 means H or C1-6 alkyl; R5 means C1-4 alkyl, CF3, CH2OH, COOH or COO (C1-4 alkyl); R6 means H, C1-4 alkyl or CF3; R7 means CH2OH, COOH, COO (C1-4 alkyl), CONR8R9 or CH2NR8R9; R8 means H, C1-6 alkyl, phenyl, phenyl- (C1-6 alkyl), COR10, COOR10, CHO, CONH2, CONHR10, SO2- (C1-6 alkyl), SO2-phenyl, and may be substituted once or twice the phenyl group with Cl, F, CF3, C1-4 alkyl, OH and / or C1-4 alkoxy; R9 means H or C1-6 alkyl; or R8 and R9 taken together, mean a C4-6 alkylene group; R10 means C1-6 alkyl, C5-7 cycloalkyl, aryl, heteroaryl, aralkyl or heteroaryl- (C1-6 alkyl); representing the aryl groups of the radicals R2 and R10 phenyl or naphthyl, representing the heteroaryl, pyrrole, pyrazol, imidazole, furanyl, thienyl, pyridine or pyrimidine groups, and may be substituted in each case, once or several times, with Cl, F , CF3, C1-4 alkyl, OH, HSO3-O- or C1-4 alkoxy, as well as their salts by the addition of pharmacologically acceptable acids and glycosides and o-sulfates; and at least one pharmacologically acceptable adjuvant, characterized in that the tablet contains at least one wetting agent. This pharmaceutical formulation, applicable orally, releases the active ingredient of formula (1) relatively quickly and completely and, therefore, leads to a high bioavailability of this active ingredient. In addition, it is characterized by good handling during the manufacturing process and thus allows technical preparation in a reproducible way and with invariably high quality. Procedure for the preparation of the tablets described above, as well as their use for the preparation of a drug intended for the treatment or prevention of arthritis, asthma, chronic obstructive pulmonary conditions, psoriasis, ulcerative colitis, disease of Alzheimer's, shock (schock), reperfusion / ischemia lesions, cystic fibrosis, atherosclerosis and multiple sclerosis.