The generation of novel unstable active chemical species and their synthetic equivalents can be attained by novel and characteristic reactions of stable organosilicon compounds which are easily designed and prepared. On the basis of this concept, syntheses of synthetic equivalents such as highly functionalized new 1, 3-dipolar reagents and thio carbanions can be applied to synthetic chemistry. Reactions of these species with a variety of dipolarophiles, heterodipolarophiles and electrophiles are found to afford functionalized heterocycles and their synthetic intermediates in highly regio- and stereoselective mode. This "tailor-made" methodology directed toward highly selective organic synthesis is described.
Molecular states of drug molecules in cyclodextrin solid dispersion systems have been studied. The possibility of inclusion compound formation was investigated between drug and cyclodextrin molecules by grinding, sealed heating and freeze drying. Solid state fluorescent spectroscopic measurements were made on the ground mixtures as well as infrared and photoacoustic spectroscopies. It was found that time resolved solid state fluorescence analysis was effective to investigate the molecular states of fluorescent probe dispersed in cyclodextrins. Sealed heating of drug-cyclodextrin mixture was recognized as a new unique method for preparing cyclodextrin inclusion compound. In the case of freeze drying, the freezing conditions showed great influences on the drug dispersion states and the crystallinity of the products. The results are explained in terms of the inclusion compound formation by grinding, sealed heating and freeze drying.
The effects of 5 crude drugs (Myricae Cortex, Polygoni Avicularis Herba, Hyperici Erecti Herba, Forsythiae Fructus, Desmodii Herba) on subacute and chronic hepatic injuries induced by carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT) were investigated in rats. All of these crude drugs suppressed significantly the increase of several biochemical parameters with CCl4-injection twice per week for 4 weeks. Polygoni Avicularis Herba and Desmodii Herba among 5 crude drugs also protected the subacute hepatic injury induced by ANIT-injection for 4 weeks. In addition, the therapeutic effect of Desmodii Herba on the chronic hepatic injury induced by CCl4-injection for 9 weeks was recognized. Desmodii Herba has protective effects on the acute and subacute hepatic injuries induced by CCl4 or ANIT and an improving effect on the chronic injury induced by CCl4. Though the increase of hydroxylproline content in the liver began 4 weeks after the CCl4 or ANIT treatment, every crude drug had no significant effect against the liver fibrosis in these study.
Effects of 50% ethanolic extracts from the liver and the gall bladder of Naja naja kaouthia LESSON (COB-L or COB-G) were studied on the phagocytic activity of a mouse reticuloendothelial system. The clearancerate of carbon was shortened by the oral administration of COB-L or COB-G (50 or 200 mg/kg). COB-L or COB-G promoted the phagocytosis of latex by peritoneal macrophages (Mφ). Furthermore, effects of these extracts on the peritoneal Mφ were biochemically investigated using in vitro experimental models. The activities of two lysosomal enzymes, acid phosphatase and β-glucuronidase, and that of lactate dehydrogenase in the peritoneal Mφ were enhanced when the Mφ were cultured with COB-L or COB-G (10-100 μg/ml) for 4 d. In addition, the consumption of glucose in the culture media by the Mφ was also enhanced by culturing the media with COB-L or COB-G. When COB-L and COB-G were given orally immediately before and 16 h after the application of picryl chloride (PC) or sheep red blood cell (SRBC), these extracts at a dose of 200 mg/kg did not show any inhibitory effects on the swelling by picryl chloride-inducing contact dermatitis (PC-CD) and by sheep red blood cell delayed type hypersensitivity (SRBC-DTH) in mice. However, these extracts inhibited the immunosupression with the SRBC 1×109 cells priming and with the freezed and dried ascites of Ehrlich carcinoma-bearing mice containing immunosupressive substances (EC-sup). These results suggest that COB-L or COB-G biochemically activates the mouse peritoneal Mφ, and promotes the phagocytic activity of the Mφ and the interaction between Mφ and T cell.
The percutaneous absorption of drug from the α-olefin oligomer (α-OL) gel base prepared by using palmitate of dextrin (Rheopearl [O!R] KL) as a gelling agent was investigated by using the abdominal skin of rats in vivo. The 20, 30, 40 and 50α-OLs with average molecular weights of 288, 380, 440 and 535, respectively were used in this study. The flurbiprofen (FP) was selected as a model drug. The percutaneous absorption of FP from the α-OL gel base was observed to be influenced by the molecular weight of α-OL. The percutaneous absorption profiles of FP from 40 and 50α-OLs gel bases were almost the same. On the other hand, the absorption of FP from 30α-OL gel base was significantly higher than those of 40 and 50α-OLs gel bases. Furthermore, the percutaneous absorption of FP from 20α-OL gel base was observed to be the highest in the test gel bases. In order to establish the reason for the differences in the percutaneous absorption of FP from 20, 30, 40 and 50α-OLs gel bases, the apparent partition ratios of FP between water and four different α-OLs were determined as a parameter of the affinity of FP for the vehicle. Consequently, it has become apparent that the partition ration exerts an influence on the percutaneous absorption of FP from the α-OL gel bases.
Quenching effects of anthraquinones on the extra-weak chemiluminescence (CL) derived from lipid peroxidation in rat brain homogenates were investigated. Such anthraquinone derivatives as emodin, rhein, and alizarin quenched the CL, while anthraquinone did not quench the CL. A linear relationship between CL-quenching activity and inhibitory rate of malondialdehyde production of various compounds was demonstrated. This technique is useful for the screening method of antioxidants.
The morphological properties of poly (β-hydroxybutyric acid) (PHB) or poly (L-lactic acid) microspheres loading flomoxef sodium (FMOX) were investigated with regard to FMOX release. The release profiles of FMOX from the microspheres could be divided into two types, a sustained release type and a burst one. Two representative PHB microspheres, the release profiles of which were quite different from those of FMOX, were compared in detail from a morphological point of view. The shapes of their surfaces and sections were observed by using scanning electron microscopy (SEM), and FMOX distribution was analyzed by using electron probe microanalysis. The crystallinity of polymers was further measured by powder X-ray diffratometry. There was little difference in the FMOX distribution and their microscopic properties such as sphere size, specific surface area, shape of surface and section. In contrast, water penetration into the inside of the microspheres was found to be clearly different by use of cryogenic SEM. A significant difference was also observed in the crystallinity of polymers froming the microspheres. The release of FMOX from the microspheres was affected by the crystallinity of polymers forming the microspheres, and burst phenomena occurred in case the polymer was highly crystallized. It was speculated that the crystallization of polymer induced micro voids in the microspheres which functioned as channels for water penetration.
The reactions of guaiazulene with 2, 4, 6-trichloro-1, 3, 5-triazine and 3, 6-dichloropyridazine gave triazinyl- and pyridazinylguaiazulenes in 52% and 60% yields, respectively. The reduction of the triazinyl derivative with sodium borohydride yielded a ring-opening product. But, the same reaction of the pyridazinyl derivative with sodium borohydride yielded an unreduced product which was cyclized between β-carbon of pyridazine ring and 4-methyl group in guaiazulene.