EMR

The commercial possibiUties for epoxy resins were first recognized by DeTrey Emres in Switzerland and DeVoe and Raynolds in the United States (1,2). In 1936, DeTrey Emres produced a low melting bisphenol A-based epoxy resin that gave a thermoset composition with phthaUc anhydride. Apphcation of the hardened composition was foreseen in dental products, but initial attempts to market the resin were unsuccessful. The patents were hcensed to CIBA AG of Basel, Switzerland (now CIBA-GEIGY), and in 1946 the first epoxy adhesive was shown at the Swiss Industries Eair and samples of casting resin were offered to the electrical industry. 

Equiactive close ratios, ratios of molar concentrations of drug (usually agonists) that produce the same response in a given system also referred to as EMR and EPMR see Chapter 10.2.3. 

Equiactive (equieffective) molar concentration (potency) ratios (EMR, EPMR), variants of the term dose ratio or equiactive dose ratios. Usually pertaining to agonists, these are the molar concentrations that produce the same response in a given system. These ratios are dependent on the affinity and efficacy of the agonists and thus are system independent, that is, characterize agonists and receptors in all systems. Care must be taken that the maximal responses of the agonists concerned are equal. 

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

In this case study, an enzymatic hydrolysis reaction, the racemic ibuprofen ester, i.e. (R)-and (S)-ibuprofen esters in equimolar mixture, undergoes a kinetic resolution in a biphasic enzymatic membrane reactor (EMR). In kinetic resolution, the two enantiomers react at different rates lipase originated from Candida rugosa shows a greater stereopreference towards the (S)-enantiomer. The membrane module consisted of multiple bundles of polymeric hydrophilic hollow fibre. The membrane separated the two immiscible phases, i.e. organic in the shell side and aqueous in the lumen. Racemic substrate in the organic phase reacted with immobilised enzyme on the membrane where the hydrolysis reaction took place, and the product (S)-ibuprofen acid was extracted into the aqueous phase. 

Table 5.1 presents the intrinsic kinetic parameters (Km and Vln lx) for the free lipase system and apparent kinetic parameters (K and V ) for the immobilised lipase in the EMR using fixed 2g-l 1 lipase concentration. The immobilised lipase showed higher maximum apparent reaction rate and greater enzyme-substrate (ES) affinity compared with free lipase. 

The inhibition analyses were examined differently for free lipase in a batch and immobilised lipase in membrane reactor system. Figure 5.14 shows the kinetics plot for substrate inhibition of the free lipase in the batch system, where [5] is the concentration of (S)-ibuprofen ester in isooctane, and v0 is the initial reaction rate for (S)-ester conversion. The data for immobilised lipase are shown in Figure 5.15 that is, the kinetics plot for substrate inhibition for immobilised lipase in the EMR system. The Hanes-Woolf plots in both systems show similar trends for substrate inhibition. The graphical presentation of rate curves for immobilised lipase shows higher values compared with free enzymes. The value for the... 

TABLE 5.1. Kinetic parameters for EMR and free lipase system... 

Fig. 5.15. Substrate inhibition plots for EMR system with top left corner showing the concentration of substrate inhibitor designated by [5 ] (Left Hanes-woolf Right Curve fit).

The 2-ethoxyethanol was a by-product, as shown in Figure 5.13. The formation rate of 2-ethoxyethanol was the same as the conversion rate of the (S)- or (R)-ibuprofen ester one mole of 2-ethoxyethanol was formed when one mole of ester was catalysed. A known concentration of 2-ethoxyethanol was added in the organic phase before the start of the reaction for product inhibition. The plots of the kinetics for the free lipase system are presented in Figure 5.17 and immobilised enzyme (EMR) in Figure 5.18, respectively. The Kw value was 337.94 mmoFl 1 for the free lipase batch system and 354.20 mmoll 1 for immobilised... 

The plotting of Dixon plot and its slope re-plot (see 5.9.5.9) is a commonly used graphical method for verification of kinetics mechanisms in a particular enzymatic reaction.9 The proposed kinetic mechanism for the system is valid if the experimental data fit the rate equation given by (5.9.4.4). In this attempt, different sets of experimental data for kinetic resolution of racemic ibuprofen ester by immobilised lipase in EMR were fitted into the rate equation of (5.7.5.6). The Dixon plot is presented in Figure 5.22. 

As an example for continuous process design, 2-keto-3-deoxy-D lycero-D-galacto-nonosouate (KDN) (S) has been produced on a 100-g scale from D-mannose and pyruvate using a pilot-scale EMR at a space-time yield of 375 gl d and an overall crystallized yield of 75% (Figure 10.6) [47]. Similarly, L-KDO (6) can be synthesized from L-arabinose [48]. 

These data can then be fed into electronic medical records (EMR) such as those the NHS plans to introduce throughout the UK over the next 2 years. This represents a process that will ultimately both reduce the frequency with which patients have to visit their doctor and improve health care delivery. EMR or electronic personal health records (as they are also known) have already been established, or are being established, in many European nations, such as Denmark. The United States, with its decentralized health care industry, is behind the curve in these efforts. However, in early fall of 2005, IBM and eight other IT companies that form the Technology CEO Council (TCC), including Intel, HP, Dell, Motorola, EMC, Applied Materials, NCR, and Unisys committed to adopt electronic health records based on open standards. In addition to these private sector efforts, the US Department of... 

Alberts MJ, Hademenos G, Latchaw RE, Jagoda A, Marler JR, Mayberg MR, Starke RD, Todd HW, Viste KM, Girgus M, Shephard T, Emr M, Shwayder P, Walker MD. Recommendations for the establishment of primary stroke centers. Brain Attack Coalition. JAMA. 2000 283 3102-3109. 

Marler JR, Jones PW, Emr M. Proceedings of a National Symposium on Rapid Identification and Treatment of Acute Stroke National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda, Maryland 1997. 

Figure 1.92. Dependence of the ratio /a i- on pH under the condition.s temperature = 150°C, ionic strength = 1, ES = 0.01 mol/kg HjO, ESe = 10" mol/kg H2O, and ES = Emr (total reduced sulfur content). (1) H2S-H2Se region, (2) H2S-HSe region, (3) HS -HSe region, (4) S -HSe region and (5) S2--Se - region (Shikazono, 1978b).

Gauthier S, Emre M, Farlow MR, et al. Strategies for continued successful treatment of Alzheimer s disease switching cholinesterase inhibitors. Curr Med Res Opin 2003 19 707-714. 

---