| 摘要 |
A particle consisting of a solid dispersion comprising, (a) a lipid lowering agent of formula I an N-oxide, a stereochemically isomeric form, a mixture of two or more such forms, or a pharmaceutically acceptable acid addition salt thereof, wherein A and B taken together form a bivalent radical of formula: N=CH (a), CH=N (b), CH2-CH2 (c) CH=CH (d), C(=O)-CH2- (e), CH2-C(=O)-(f), in the bivalent radicals of formula (a) and (b) the hydrogen atom may be replaced by C1-6 alkyl, in the bivalent radicals of formulae (c), (d), (e), (f), one or two hydrogen atoms may be replaced by C1-6 alkyl, R1 is hydrogen, C1-6 alkyl or halo R2 is hydrogen or halo, R3 is hydrogen, C1-8 alkyl, C3-6 cycloalkyl or C1-8 alkyl substituted with hydroxy, oxo, C3-6 cycloalkyl or aryl, Het is a heterocycle selected from the group consisting of pyridine, pyridine substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6 alkyl)amino or aryl, pyrimidine, pyrimidine substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6alkyl)amino or aryl, tetrazole, tetrazole substituted with C1-6 alkyl or aryl, triazole, triazole substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6 alkyl)amino, thiadiazole, thiadiazole substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6 alkyl)amino, oxadiazole substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6 alkyl)amino, imidazole, imidazole substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6alkyl)amino, thiazole, thiazole substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6 alkyl)amino, oxazole, oxazole substituted with one or two substituents selected from C1-6 alkyl, hydroxy, C1-6 alkyloxy, trihalomethyl, amino, mono or di(C1-6 alkyl)amino, aryl is phenyl or phenyl substituted with C1-6 alkyl or halo, and (b) one or more pharmaceutically acceptable water-soluble polymers. Also described is the use of the abovementioned particles in the manufacture of pharmaceutical dosage forms for treating hyperlipidemia, obesitas and atherosclerosis. Such dosage forms can be administered once daily, and in addition at any time of the day. These particles are obtained by melt-extruding a mixture comprising a lipid lowering agent and an appropriate water-soluble polymer and subsequently milling said melt-extruded mixture.
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