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SynopsisA method to determine the concentration of t-aminocaproic acid (ACA) in poly-t-caprolactam by high-pressure liquid chromatography is established. The polymerizations for initial water concentrations of 0.42,0.82, and 1.18 mol/kg and temperatures of 230,240,250,260,270, and 280°C were performed and concentration-versus-time curves were obtained for ACA, c-caprolactam (CL), and endgroups (EG). Each curve for ACA and EG has a maximum which increases monotonically in its value and shifts from right to left in position with increasing either the temperature or the initial water concentration. The reaction rates of CL, EG, and ACA were also evaluated numerically from the concentration data. The observed kinetic data were compared with those obtained by the numerical solution of the rate equations with Reimschuessel's kinetic constants. Good agreement is found in C L and EG concentrations but discrepancies in ACA concentration and rates are considerable, particularly in the early stage of the polymerization.

AMG 531 is a novel thrombopoiesis-stimulating peptibody being investigated for the treatment of chronic immune thrombocytopenic purpura. This double-blind, phase I study evaluated the safety, pharmacodynamics, and pharmacokinetics of AMG 531 in healthy Japanese men. Thirty subjects were randomly assigned 4:1 (AMG 531/placebo) to receive 1 dose of AMG 531 (0.3, 1, or 2 microg/kg) or placebo by subcutaneous injection; subjects were evaluated for 6 weeks. AMG 531 was generally well tolerated, with adverse events similar to placebo. Treatment-related adverse events (headache, "feeling hot," malaise) were reported for 5 of 24 AMG 531-treated subjects. Platelets generated after exposure to AMG 531 functioned normally. Four of 8 subjects receiving 1 microg/kg and 7 of 8 receiving 2 microg/kg had platelet count increases > or =1.5-fold over baseline, an effect similar to that seen in non-Japanese subjects. Serum AMG 531 concentrations were below the lower limit of quantification in all but 2 subjects receiving 2 microg/kg.

SynopsisThe concrete simulation models dealiig with the kinetic behavior of the hydrolytic polymerization of e-caprolactam (CL) in various polymerization reactors used in the industry were described, and the method for their numerical solutions was presented. The characteristic data of the polymerization such as the concentrations of CL, end group, water, c-aminocaproic acid, cyclic dimer, and the hot-water-soluble component, conversion, number average, and weight average molecular weights, and solution and melt viscosities can be calculated at every stage of the polymerization reaction, at every part of the reactors, and/or at the outlet of the reactors. The calculated values based upon the models were found to be quite compatible with the observed values for the reactors. The applicability of the technique was well confirmed for the quality control, process control, modification of existing plants, and development of new chemical process plants.

SynopsisThe kinetic and thermodynamic constants of the hydrolytic polymerization of c-caprolactam were determined by least-squares curve fitting. The calculations were carried out using observed kinetic data such as concentrations of c-caprolactam ([CL]), endgroup ([EG]), and e-aminocaproic acid ([ACA]) and time derivatives of each concentration (rates) d[CL]Idt, d[EG]/dt, and d[ACA]Idt.The sets of the converged constants are obtained for the initial water concentrations of 0.42,0.82, and 1.18 molekg. An averaged set of the constants applicable for this range of the initial composition was also evaluated. The compatibility between observed and calculated concentration and rate curves was improved by the use of the newly developed sets of the constants. The mechanism of the polycondensation reaction is also discussed, based on the rate and kinetic constants obtained by this work. HYDROLYTIC POLYMERIZATIONThe hydrolytic polymerization of e-caprolactam (CL) has been studied by variousThe proposed reaction mechanism, the set of the rate equations derived from the mechanism, and the kinetic and thermodynamic constants are summarized in Table I. Here, x , y , z, and w are the concentrations of CL, endgroup (EG), e-aminocaproic acid (ACA), and water, respectively; kj is the rate constant; Ki is the equilibrium constant; A{ is the frequency factor;