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  • Chemical Engineering  (4)
  • Organic Chemistry  (3)
  • 1995-1999  (7)
  • 1996  (7)
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ibutilide and its enantiomers in dogs (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 8 (1996), S. 18-23 
    Details
    ISSN: 0899-0042
    Keywords: racemate ; enantiomer ; bioavailability ; pharmacokinetic ; ibutilide ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ibutilide fumarate, a new drug for the treatment of cardiac arrhythmias, contains a stereogenic center bearing a secondary alcohol group. Several single dose and multiple dose studies of racemic ibutilide or its enantiomers were performed by the oral and intravenous routes in dogs. A chiral assay was used to examine racemization and the individual enantiomer pharmacokinetics. Following low oral or intravenous doses (approximately 0.3 mg/kg), the pharmacokinetics of the enantiomers were nearly identical, with no substantial chiral conversion. Both enantiomers exhibited high clearance rates, large volumes of distribution, and low oral bioavailability. As the dose increased, pharmacokinetic differences between the enantiomers were observed. The greatest differences (3-fold) were seen after oral administration at 4 mg/kg, indicating that first-pass metabolism of ibutilide was highly enantioselective at high doses. The clearances of the enantiomers differed by up to 34% at 5 mg/kg followed intravenous administration of the racemate. At high doses, other non-linear pharmacokinetic behavior was also apparent. The intravenous clearance of ibutilide declined from 5.3 L/h/kg at 0.3 mg/kg to 3.7 L/h/kg at a dose of 5 mg/kg. The absolute oral bioavailability of the racemate increased from 2% at 0.3 mg/kg to as much as 84% at 5 mg/kg. © 1996 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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    Paper (German National Licenses)
  • 2
    Electronic Resource
    Electronic Resource
    Transport phenomena and kinetics in an extravascular bioartificial pancreas (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 2668-2682 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A bioartificial pancreas, consisting of immobilized islets encapsulated within hollow fibers, is investigated as an alternative treatment for insulin-dependent diabetes. A mathematical model is developed to determine whether this configuration of the bioartificial pancreas can yield an insulin response to a glucose challenge with the appropriate dynamics in diabetic humans. The model consists of the 2-D mass-conservation equations for glucose and insulin within the hollow fiber and capillaries. The equations contain terms for insulin-production kinetics by porcine islets and glucose-consumption kinetics. The boundary conditions account for transport resistances of the fiber membrane, the tissue surrounding the implant, and a thin film within the capillaries. The equations are coupled to a pharmacokinetic model of the circulatory system. The calculations show that an optimized design with this configuration will be feasible for human use and requires a total volume of 4.6 mL to reach the target insulin concentration in the bloodstream following a glucose challenge. The parameters and processes controlling the system performance are discussed.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420928
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  • 3
    Electronic Resource
    Electronic Resource
    Statistical operating strategies for charging batch reactors (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1304-1318 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Two critical decisions must be made in the charging sequence of batch reactors: target setting and alarm generation. A number of statistics-based strategies are proposed in this article to perform these tasks. The off-line and on-line target setting procedures developed in this work can be adopted to increase the profit margin of any given batch process without sacrificing reliability. A synthesis method for building optimal alarm logic is also described in detail. Monitoring systems constructed according to this suggested approach are effective in reducing the probability of undetected faulty batches. Extensive simulation studies show that the proposed strategies are suitable for application of manufacturing high-value-added products, which is a prevailing practice in batch processes.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420511
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  • 4
    Electronic Resource
    Electronic Resource
    Kinetics of silica particle formation in nonionic W/O microemulsions from TEOS (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 3153-3163 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The kinetics of silica particle formation by the ammonia-catalyzed hydrolysis of tetraethyl orthosilicate (TEOS) in water-in-oil (W/O) microemulsions containing a nonionic surfactant was investigated using Fourier-transform infrared spectroscopy, transmission electron microscopy, and light-scattering techniques. The results show that TEOS hydrolysis and silica-particle growth occur at the same rate, indicating the growth of silica particles is rate-controlled by the hydrolysis of TEOS. The rate of TEOS hydrolysis in microemulsions is first order with respect to the concentration of aqueous ammonia (29 wt. % NH3), but depends weakly on the concentration of water. Based on the fact that TEOS hydrolysis follows a nucleophilic (SN2) substitution of the TEOS's ethoxy group with hydroxyl ion, the kinetic data suggest that both water and ammonia remain predominately in W/O microemulsion droplets. The rate of TEOS hydrolysis also depends on the surfactant concentration that controls the molecular contact between hydroxyl ions and TEOS in the solution. Due to the reaction-controlled growth mechanism, the silica-particle size distribution retains virtually the same shape over the growth period. The final average size of silica particles can be varied from 26 to 43 nm by adjusting concentrations of water and surfactant. Increasing the water concentration decreases the average size and uniformity of silica particles. For a given water concentration, the smallest and most uniform silica particles are produced at intermediate water-to-surfactant molar ratios (about 1.9). The results are discussed in terms of the effect of water concentration on the stability of the hydrolyzed silica reacting species during the nucleation of particles and of the water-to-surfactant molar ratio on the compartmentalization of silica species in microemulsions.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690421115
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  • 5
    Electronic Resource
    Electronic Resource
    Simulation of noise-driven wave dynamics on a falling film (1996)
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 42 (1996), S. 1553-1568 
    Details
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A numerical model developed simulates inlet noise-driven wave dynamics on a falling film at relatively high Reynolds numbers. Two parameters, a normalized Reynolds number and a noise index, are sufficient to specify the wave statistics on most channels. Observed phenomena, like wave inception, downstream wave texture coarsening, initial deceleration and subsequent acceleration of wave speeds, are quantitatively reproduced and explained. Statistical analysis from our simulations suggests that beyond a critical Reynolds number this complex noise-driven spatio-temporal dynamics can be modeled by a deterministic interaction theory based on stable solitary waves that resemble onehump pulses and a statistical theory with a random-phase description of noise. The “chaotic” wave dynamics at higher Reynolds number is hence due to both noise amplification/filtering and intrinsic dynamics.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aic.690420607
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  • 6
    Electronic Resource
    Electronic Resource
    Synthesis of Coumarin Derivatives as Inhibitors of Platelet Aggregation (1996)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 79 (1996), S. 651-657 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In a search for the inhibitors of platelet aggregation, certain coumarin derivatives were synthesized and evaluated for antiplatelet activity against thrombin(Thr)-, arachidonic acid(AA)-, collagen(Col)-, and platelet-activating-factor(PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from 4-hydroxycoumarin (1) or naphthalen-1-ol via alkylation and Reformatsky-type condensation (Schemes 1-3). Among them, 4-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy]-2H-1-benzopyran-2-one (6b) showed potent antiplatelet effects on AA- and PAF-induced aggregation with IC50 values of 8.21 and 103.67 m̈M, respectively (see Tables 1 and 2). The antiplatelet potency of 6b against PAF-induced aggregation could be further improved by introducing a proper substituent at the 2-phenyl group of the lactone ring.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19960790308
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  • 7
    Electronic Resource
    Electronic Resource
    Antiplatelet α-Methylidene-γ-butyrolactones: Synthesis and evaluation of quinoline, flavone, and xanthone derivatives (1996)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 79 (1996), S. 1620-1626 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: As a continuation of our previous studies on the synthesis and antiplatelet activity of coumarin derivatives of α-methylidene-γ-butyrolactones, certain quinoline, flavone, and xanthone derivatives were synthesized and evaluated for antiplatelet activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from quinolin-8-ol, flavon-7-ol, and xanthon-3-ol, respectively, via alkylation and Reformatsky-type condensation (Schemes 1-3). By the comparison with comparison with coumarin α-methylidene-γ-butyrolactone 3a, flavone and xanthone derivatives, 3b and 3c, respectively, are more selective in which only AA- and collagen-induced aggregation are strongly inhibited. Most of the quinoline derivatives (9a-e) exhibited broad-spectrum antiplatelet activities.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19960790612
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