Assay of α-glucosidase inhibitory activity using flow-biosensor system

A convenient and continuous method for the assay of α-glucosidase (AGH) inhibitory activity was developed using a continuous-flow/stopped-flow system combined with biosensors. The amount of glucose liberated from maltose by the action of AGH was quantified by an immobilized glucose oxidase (GOD) reactor with a Clark oxygen sensor in the downstream. The immobilized AGH reactor was set in the flow-line. When an inhibitor containing 10 mM maltose substrate was injected and as it reaches the center of the immobilized AGH reactor, the working solution (synthetic intestinal fluid) was stopped for a certain period. After the reaction of inhibitor and/or substrate with AGH, the working solution was propelled again, and the glucose liberated was passed through the immobilized GOD reactor. The inhibition ratios (%) were calculated as the percent inhibition, which were the glucose concentrations in the presence of maltose and inhibitor divided by those in the presence of maltose alone. The multi-channel stopped-flow (MCSF) system was also developed, in which a seven-port, six-positioned rotary valve was inserted and six immobilized AGH reactors were set in a parallel configuration. The IC₅₀ values of acarbose and 1-deoxynojirimycin, a medicinal inhibitor for diabetes, were 0.46±0.062 and 0.23±0.031 μM, respectively, and coincided well with those by our pseudo-in vivo method [Biol. Pharm. Bull. 232 (2000) 1084]. The time to assay the inhibitory activity of one unknown sample was estimated to be 11 min by the 6-channel modified-MCFS system. The proposed MCFS system offers a useful method to evaluate the inhibitory activity for AGH.     

Convolution equivalence and distributions of random sums

A serious gap in the Proof of Pakes’s paper on the convolution equivalence of infinitely divisible distributions on the line is completely closed. It completes the real analytic approach to Sgibnev’s theorem. Then the convolution equivalence of random sums of IID random variables is discussed. Some of the results are applied to random walks and Lévy processes. In particular, results of Bertoin and Doney and of Korshunov on the distribution tail of the supremum of a random walk are improved. Finally, an extension of Rogozin’s theorem is proved.     

Polymer combination increased both physical stability and oral absorption of solid dispersions containing a low glass transition temperature drug: physicochemical characterization and in vivo study

The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (T(g)) and poorly water-soluble drug. Drug/polymer blends with differing physicochemical stabilities and oral absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically increased the drug oral absorption property, while PVP-VA or PVP stabilized solid dispersions during storage by increasing the T(g) in proportion to polymer concentration. Experimental T(g) values corresponded closely with theoretical T(g) values; indeed, the T(g) values of solid dispersion with HPMC did not increase significantly compared to the T(g) value for the drug alone. A solid dispersion formulation incorporating two different polymers-HPMC and either PVP-VA or PVP-maintained increased T(g), physicochemical stability, solubility, and bioavailability of the solid dispresions owing to each polymer. These findings suggested that both oral absorption and physicochemical stability of low-T(g) drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.     

A simple way to acquire T(1)-weighted MR images of rat liver with respiratory triggering

To acquire high-resolution T(1)-weighted images of the liver in rats, for which breath-holding cannot be ensured, respiratory triggering is essential. At the respiratory rate of 30-60 times/min in rats, however, T(1)-weighted images cannot be obtained with simple triggering. As a simple solution to this, we applied multiple repeated acquisitions with one trigger signal. With this technique, sufficient T(1) contrast could be easily achieved in rat liver enhanced by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid infusion.     

Novel cyclization reaction of 1,omega-diiodo-1-alkynes without the loss of iodine atoms

In the presence of 1-hexynyllithium (0.2-0.6 equiv.), 1,omega-diiodo-1-alkynes undergo a new type of cyclization reaction without the loss of two iodine atoms to afford (diiodomethylene)cycloalkanes.     

Improvement in Solubility of Poorly Water Soluble Drug by Cogrinding with Highly Branched Cyclic Dextrin

We investigated the enhancement of the solubility of glibenclamide (GCM), a poorly water soluble anti-diabetes drug, by cogrinding it with highly branched cyclic dextrin (HBCD) using a ball mill. Highly branched cyclic dextrin (HBCD) is a novel cyclic glucan produced from waxy corn starch by the cyclization reaction of a branching enzyme. When GCM crystals were coground with HBCD for 2 h, the solubility of GCM was improved to 12.4 μg/ml, while the concentration of HBCD was 5.0 mg/ml. Additionally, the GCM solubilized with HBCD was chemically stable in aqueous solution for at least 1 week at room temperature. The peak intensity assigned to crystalline GCM disappeared after cogrinding it by observing its powder X-ray diffraction pattern, which means that the crystalline structure of GCM could be disrupted. In the DSC measurement, the ground mixture showed a single endothermic peak, even though a temperature depression of the endothermic peak due to GCM crystal was observed. After the cogrinding, two sharp peaks assigned to sulfonylurea and benzoyl carbonyl stretching bands varied to broaden the peak to around 1640 cm⁻¹ in the C=O stretching region. These results suggested the formation of solid dispersion between GCM and HBCD.     

A nonaqueous potentiometric titration study of the dissociation of t-butyl methacrylate-methacrylic acid copolymers.

The dissociation of t-butyl methacrylate-methacrylic acid copolymers in dimethyl sulfoxide was analyzed by a nonaqueous potentiometric titration technique. The negative logarithm of the dissociation constant of the monomer unit of a methacrylic acid (MAA) monotonously increased with the increasing degree of dissociation corresponding to the titrant/MAA amount ratio, and was highly influenced by the copolymerization ratio. The results are discussed in terms of the suppression of the dissociation of MAA by a neighboring charged methacrylate anion unit.