The components of Artemisia and Labiatae species were isolated and their chemical structures were determined. These compounds were found to have tannic activity for the first time. The activity of the compounds comes from the caffeic acid moiety in their molecules, not from structural features of usual tannins (hydrolyzable and condensed tannins). These also showed several other biological activities. Furthermore, the research on dimerization of caffeic acid derivatives was performed.
Morphine is a potent analgesic and is widely used in the clinical management of severe acute and chronic pain; however, its clinical usefulness is limited due to the developement of both tolerance and dependence after repeated morphine administration. The morphine metabolism has been studied in order to elucidate its pharmacological actions as well as its adverse effects. Thus far several metabolites have been identified and their analgesic potency and toxicity have been also investigated. In the toxicological viewpoint, the production of reactive metabolites that can bind cellular glutathione and protein has been postulated. We found morphine 6-dehydrogenase, which catalyzes the dehydrogenation of 6-hydroxy group of morphine to produce morphinone, in the guinea pig liver. It was also found that morphinone antagonizes the morphine analgesia and binds with glutathione and protein. We here demonstrate the presence of a metabolic pathway of morphine to morphinone and subsequently to morphinone-glutathione adduct, and compare the property including primary structure among the guinea pig, rabbit, mouse and hamster liver morphine 6-dehydrogenases. We also describe the toxicological significance of morphinone.
From the need of a new infomation tool for the simple and accurate understanding of drug usage by patients, we developed an on-line system that printed information sheets on drug usage with color illustrations based on the physician's instructions, and gave the documents to the patients. In this system, documents with color illustrations explaining how to use drugs could be registered for each drug which is difficult to be used or for each patient. This has made it possible to provide accurate information on drugs not only to patients who have difficulty in understanding prescription data given by doctors but also to those who have difficulty in understanding oral explanation of the regimen. Also, the authors distributed draft explanatory documents prepared in advance to doctors and nurses asking for their opinions about them to avoid discrepancy between the explanation on the clinical scene and the contents of the documents. From a questionnaire survey completed by 74 patients before starting this system, the documents with color illustrations, explaining about the side effect and usage of inhalation, suppository and eye drops, obtained a good response in terms of understanding and reconfirmation. After starting the system, 68 patients prescribed for colon examinations (colonoscopy and barium enema) also replied that the documents are recognizable. These results suggest that this system is useful to prevent incorrect usage of drugs and is helpful for drug use evaluation.
The inhibitory effects of hybrid liposomes composed of lipids having a variety of head groups (zwitterionic L-α-dimyristoylphosphatidylcholine (DMPC), anionic L-α-dimyristoylphosphatidylglycerol (DMPG), and cationic 1, 2-dimyristoyl-3-trimethylammonium propane (DMTAP)) and polyoxyethylene (10) dodecyl ether (C12(EO)10) on the growth of tumor cells (human lung carcinoma (RERF-LC-OK), human hepatoma (Hep-G2), human stomach tumor (GT3TKB)) in vitro were examined. The hybrid liposomes of DMPC/10 mol % C12(EO)10 and DMPG/10 mol % C12(EO)10 were fairly more effective for inhibiting the growth of all tumor cells employed in this study as compared with liposomes (DMPC and DMPG) or micelles (C12(EO)10). Especially, it is attractive that the highly specific inhibitory effect of the hybrid liposomes of DMPG/10 mol % C12(EO)10 without any antitumor drugs on the growth of RERF-LC-OK and GT3TKB was obtained for the first time.
Capillary electrophoresis (CE) has been utilized as a tool for enantiomeric separation. It has been incorporated into both USP and EP forums as the methods for general tests and assays. In the present study, we applied CE to the assay and content uniformity of denopamine tablets (KALGUT[○!R]), which are clinically used as a cardiotonic agent. The electrophoretic solution consisted of phosphate buffer of pH 2.5 containing 2, 6-di-O-methyl-β-cyclodextrin (DM-β-CD) to achieve enantiomer separation, because denopamine is an optically active drug. During this study, we found that the purity of the positional isomerism of DM-β-CD, significantly influenced the resolution of denopamine enantiomers. This effect of isomer purity was also confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometer analysis. The results of the assay and system suitability test indicated that CE method could be useful as an alternative to the conventional HPLC method.