Utilization of quinolone drugs as monomers: characterization of the synthesis reaction products for poly(norfloxacin diisocyanatododecane polycaprolactone).
A broad spectrum antimicrobial agent, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (norfloxacin), has been successfully incorporated as a monomer into a polyurethane backbone structure via a three-step polymerization of norfloxacin, diisocyanatododecane (DDI), and polycaprolactone diol (PCL). The reaction was catalyzed by dibutyltin dilaurate and carried out in dimethyl sulfoxide. The sequential order of monomer feeding had a strong influence on the polymerization behavior and final polymer structure. In the preferred reaction scheme norfloxacin is initially reacted with DDI to form an oligomer. This is followed by a second reaction where PCL is introduced in order to produce a drug polymer chain with higher molecular weight and degradable segments. Cross-linking of urea linkages between the norfloxacin and DDI segments was a particular concern and was minimized by feeding PCL into the reaction system immediately following the completion of the first step. Chain extension by 1,4-butanediol or ethylenediamine was shown to be an effective approach for increasing the molecular weight of the polymers.
Yang
M
M
Department of Diagnostics and Biological Sciences, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, Canada M5G 1G6.
Santerre
J P
JP
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002850:Chromatography, Gel; D017953:Isocyanates / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D013997:Time Factors
C469549:1,12-diisocyanatododecane; D000890:Anti-Infective Agents; D017953:Isocyanates; D011091:Polyesters; C016240:polycaprolactone; D009643:Norfloxacin