An improved wound dressing with a long-term drug diffusion-efficacy has been developed by UV-radiation technique. It involves incorporation of ciprofloxacin (CIP), at the concentration of 0.5-2.0% (w/v), into a water mixture of 2-hydroxymethacrylate (HEMA) monomer, benzoin isobutyl ether (BIE) initiator and different content of ethylene glycol dimethacrylate (EGDMA) cross-linker. Increasing the concentration of EGDMA would reduce the releasing ratio of CIP from pHEMA. T1/2 is increased from 2.64 to 45.67 h when the EGDMA is added from 1 to 8%. In the ranges of 0< or = F < or = 0.6, the n value of 1%CIP-pHEMA membranes is increased from 0.48 to 0.81. It indicates that the mechanism of drug release falls between the Fickian and Case II diffusion model. The antibacterial activity of the drug impregnated into the membrane was evaluated by in vitro drug kinetic agar plate method. Higher concentration of EGDMA, up to 8% of the cross-linker, extends the drug release. Comparison with the drug-soaked membranes, the newly synthesized 1% CIP-pHEMA membrane (cross-linked with 4% EGDMA) sustains the release of the entrapped drug and maintains the antibacterial activity up to 12 days.

A general synthesis of substituted 1,2-dihydroisoquinolines based on intramolecular 1,3-dipolar cycloaddition of alkyl azides and olefins is described. Reaction of bromide 4 with sodium azide afforded azide 5, which underwent 1,3-dipolar cycloaddition intramolecularly to give triazoline 6. Rearrangement of triazoline 6 on silica gel gave diazo compound 7. Treatment of 7 with rhodium acetate afforded substituted 1,2-dihydroisoquinoline 9 in good overall yield.

In order to obtain much slower biodegradable films, which are often required for biomedical applications, we have developed a series of studies on heterogeneous cross-linking of hyaluronic acid (HA) films by using 2-chloro-1-methylpyridinium iodide (CMPI) or 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide (EDC) as cross-linking reagents. From the in vitro degradation rate, we found that EDC cross-linked HA films completely dissolved in PBS at 37 degrees C during the period of 4-6 days. However, CMPI cross-linked HA films showed only a low percentage of weight loss over 30 days. This phenomenon could be explained from the mechanism of reaction between carboxyl group of HA and EDC. The latter reacted with carboxyl group to form an unstable intermediate O-acylurea, which showed a relatively low reactivity and quickly rearranged to form a stable N-acylurea. Thus, most of the EDC-activated carboxyl groups in HA were chemically transferred into N-acylurea or left as unreactive O-acylurea, and only a few of cross-linking bonds were formed between HA. On the other hand, the intermediate obtained from the reaction between carboxyl group and CMPI showed a relatively high reactivity and reacted with the hydroxyl group of the same and/or different molecules of HA to form an inter- and intramolecular esterification. Apparently, CMPI cross-linked HA films have a much higher cross-linking density and constructed a more rigid three-dimensional network. Therefore, it produced HA films, which dramatically increased its enzymatic stability in aqueous solution of hyaluronidase. The obtained results from elemental analyses, FT-IR spectra and NMR spectra also indicate that acylurea groups were introduced into EDC-cross-linked HA films.

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products observed in etherification of tertiary alkyl alcohols. Experimental Section12Typical Procedure for Preparation of Acyclic Ethers. To a stirred solution of -methylbenzyl alcohol (245 mg, 2.0 mmol) in dichloroethane (10 mL) at room temperature was added anhydrous zinc chloride (270 mg, 2.0 mmol). The reaction mixture was stirred at room temperature for 4 h, diluted with dichloromethane (30 mL), and washed with water and brine. The organic layer was dried over anhydrous MgS04 and evaporated to dryness.The residue was distilled with a Kugelrohr apparatus to afford bis ( -methylbenzyl) ether (206 mg, 91%) as a colorless oil. The spectral data and boiling point were identical with those of reported data.Typical Procedure for Preparation of Cyclic Ethers. To a stirred solution of 1-phenyl-1,5-pentanediol (182 mg, 1.0 mmol) in dichloroethane (20 mL) at room temperature was added zinc chloride (135 mg, 1.0 mmol), and the reaction mixture was stirred at 80 °C for 2.5 h. The usual workup and distillation with a Kugelrohr apparatus gave 2-phenyltetrahydropyran (136 mg, 84%). The spectral data13 and boiling point were in agreement with reported data.Acknowledgment. This investigation was supported in part by a grant from the Korea Science and Engineering Foundation. We are grateful to Sung Soo Kim for the experimental assistance.Registry No. PhCH(Me)OH, 98-85-1; Ph2CHOH, 91-01-0;