Formulation of sustained Release Tablets of piperazine piperidine antagonists and agonists of the receptor - 5 at the 5-ht1a Aripiprazole with improved Dissolution instestinal

摘要

The sustained release pill formula of methyldiazepine can be used for the treatment of central nervous system disorders: a preparation process, as well as the method of use. Requirement 1: a sustained release pill formula for oral characteristics Because it includes: (a) a formula compound (1),or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16, are each independently -H, alkyl- (C1-6),1. Halide (C1-6),alquenilo- (C2-6)Or tar (c2-6)Halocarbon, CF3, NO2, CN, or25, SO2, R25, sr25, so2r25, so2n (R25) 2, n (R25) 2, C (o),-Cor25, co2r25, nr25co2r25, nr25cor25, nr25con (R25) 2, o-con (R25) 2RA and Rb are respectively h-o-ch3; R25 es-h, acquilo - (C1-6) direct or branch, haloguilo - (C1-6) alquenilo - (c2-6),Or bitumen - (c2-6);(b) at least one organic acid; (c) at least one release controller; (d) at least one filler; and (e) at least one lubricant. Claim 4: The formulation of any one of claims 1 to 3, characterized in that the compound of formula (1) is selected from the group consisting of: 6-methoxy-8- [4- (1-quinolin-8-yl -piperidin-4-yl) -piperazin-1-yl] -quinoline; 6-fluoro-8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 5-fluoro-8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 7-fluoro-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1- yl) piperidin-1-yl) quinoline;6-fluoro-8- {4- [1- (8-fluoroquinolin-7-yl) piperidin-4-yl] piperazin-1-yl) quinoline; 3-trifluoromethyl-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) quinoline; 6-methoxy-8- (4- (1- (quinolin-8-ylmethyl) piperidin-4-yl) piperazin-1-yl) quinoline; 5-fluoro-4-methoxy-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) -2- (trifluoromethyl) quinoline; 5-fluoro-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) quinoline; 5-Fluoro-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) quinoline trisuccinate; 8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-jl] -quinoline; 6-chloro-8- [4- (4- (6-chloro) -quinolin-8-yl-piperidin-1-yl) -piperazin-1-yl] -quinoline;6-fluoro-8- [4- (4- (6-chloro) -quinolin-8-yl-piperidin-1-jl) -piperazin-1-yl] -quinoline; 5-chloro-8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 2-methyl-8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 6-chloro-8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 8- [4- (1-quinolin-8-yl-piperidin-4-yl) -pjperazin-1-yl] -5-trifluoromethyl-quinoline; 5-methoxy-8- [4- (1-quinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 5-fluoro-8- [4- (4-quinolin-8-yl-piperazin-1-yl) piperidin-1-yl] -quinoline; 6-methoxy-8- [4- (2-methylquinolin-8-yl-piperidin-4-yl) -piperazin-1-yl] -quinoline; 6-fluoro-8- (4- (1- (2-methylquinolin-8-yl) piperidin-4-yl) piperazin-1-yl) quinoline;- 1-1-1-1 - (1-1 -) (1-1 -) (1 (1 - (2,4-dimethyl-5-fluoroquinol-8-il) piperidin-4-il) piperazin-1-il; 2. Handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle handle;6-fluoro-8- (4- (1- (7-fluoroquinolin-8-yl) piperidin-4-yl) piperazin-1-yl) quinoline; 6-methoxy-8- {4- [1- (8-fluoroquinolin-7-yl) piperidin-4-yl] piperazin-yl} quinoline; 6-methoxy-8- {4- [1- (2-trifluoromethyl-4-methoxyquinolin-7-yl) piperidin-4-yl] piperazin-1-yl} quinoline; 6-methoxy-8- (4- (1- (2-trifluoromethyl-4-methoxyquinolin-8-yl) piperidin-4-yl) piperazin-1-yl) quinoline; 5-fluoro-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) -2-trifluoromethylquinoline; 5-fluoro-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) -3-trifluoromethylquinoline; 5-fluoro-8- (4- (4- (6-methoxyquinolin-8-yl) piperazin-1-yl) piperidin-1-yl) -4-trifluoromethylquinoline;1 - (6-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1-1 yes