YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
117 巻, 2 号
選択された号の論文の5件中1~5を表示しています
  • 澤田 康文, 山田 安彦, 伊賀 立二
    1997 年 117 巻 2 号 p. 65-90
    発行日: 1997/02/25
    公開日: 2008/05/30
    ジャーナル フリー
    For the quantitative assessment of therapeutic/pharmacologic effects and adverse/toxic effects of drugs which interact with several specific receptors, we developed an integrated pharmacokinetic analysis system by considering a receptor occupancy theory and a ternary complex model. The developed system has made it possible to predict the optimal dosage for the investigation of drugs using pre-clinical and clinical data (phase I study) under development, and to assess quantitatively the intensity of adverse/toxic effects of drugs which are not observed in the stage of clinical study. As for commercially available drugs, the developed system may be useful for planning the rational drug dosage regimen to obtain desired therapeutic effects with minimum adverse/toxic effects. Our new methodology for the rational dosage regimen of a new drug will be established based on the results of this study.
  • 宮地 弘幸, 我妻 昭彦, 橋本 祐一
    1997 年 117 巻 2 号 p. 91-107
    発行日: 1997/02/25
    公開日: 2008/05/30
    ジャーナル フリー
    Tumor necrosis factor alpha (TNF-α), an important cytokine produced mainly by activated macrophages, plays a critical role in certain physiological immune systems. But it causes severe damage to the host when produced in excess. Therefore, TNF-α can be regarded to possess both favorable and unfavorable effects. These pleiotropic effects indicated that TNF-α production-enhancers in some cases and TNF-α production-inhibitors in other cases would be useful as biological response modifiers (BRMs) under various circumstances. A possible lead compound is thalidomide, which had been used as a hypnotic/sedative agents but was withdrawn from the market because of it's teratogenicity. Thalidomide is a specific inhibitor of TNF-α production, and this effect has been shown to be useful for the treatment of various immunodiseases. Recently, we found that the regulation of TNF-α production by thalidomide and related phthalimides was both inducer-specific and cell-type-specific, i.e., (I) the compounds enhance 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced TNF-α production by HL-60 cells, while they inhibit TPA-induced TNF-α production by another human leukemia cell line THP-1, and (II) the compounds inhibit TNF-α production both by HL-60 and THP-1 cells when the cells are stimulated with okadaic acid. We also found that in a optically active phthalimide analogues of thalidomide the inducer specific bi-directional regulation of TNF-α production is separated. This implies that the target molecule (s) of the two systems are different each other.
  • 吉川 雅之, 村上 敏之, 植田 知彦, 吉積 智司, 二宮 清文, 村上 啓寿, 松田 久司, 斉藤 雅之, 藤井 互, 田中 隆治, 山 ...
    1997 年 117 巻 2 号 p. 108-118
    発行日: 1997/02/25
    公開日: 2008/05/30
    ジャーナル フリー
    The methanol-soluble fraction from a Chinese natural medicine Hoveniae Semen Seu Fructus, the seed and fruit of Hovenia dulcis THUNB. (Rhamnaceae) was found to show an inhibitory effect on the alcohol-induced muscular relaxation and a protective activity on the D-galactosamine/lipopolysaccharide or carbon tetrachloride-induced liver injury. Through bioassay-guided separation using a traction performance test, three new dihydrofravonols named hovenitins I, II, and III were isolated from Hoveniae Semen Seu Fructus together with four known flavonoids, (+)-ampelopsin, laricetrin, myricetin, and (+)-gallocatechin. The absolute stereostructures of hovenitins I, II, and III were determined on the basis of chemical and physicochemical evidence to be (2R, 3R)-5, 7, 4', 5'-tetrahydroxy-3'-methoxydihydroflavonol, (2R, 3S)-5, 7, 4', 5'-tetrahydroxy-3'-methoxy-dihydroflavonol, and (2R, 3S)-5, 7, 3', 4', 5'-pentahydroxydihydro-flavonol, respectively. Hovenitin I and (+)-ampelopsin, both of which were principal ingredients of the active fractions from this natural medicine, were found to show an inhibitory activity on the ethanol-induced muscle relaxation in rats. In addition, hovenitin I showed a protective activity on the liver injury induced by D-galactosamine/lipopolysaccharide or carbon tetrachloride in mice.
  • 山本 貴代, 桃田 道彦, 北村 久代, 成田 九州男
    1997 年 117 巻 2 号 p. 119-125
    発行日: 1997/02/25
    公開日: 2008/05/30
    ジャーナル フリー
    A study of the measurement and the data-proceeding analysis methods has been conducted in order to expand the range of the application of the differential scanning calorimeter (DSC)-based purity measurement method. Using a variety of systems that form eutectic mixtures, samples were measured by the DSC method. The heat of fusion of the melt fraction was determined including the fusion curve of the eutectic mixture. Temperature (T) versus the inverse of the melt fraction (1/F) was plotted at the inflection point on the declining side of the DSC curve at the principal component peak. The heat of fusion of the meet fraction was corrected so as to linearize the curved line of T versus 1/F. On the basis of the straightened line, the estimated values of the melting points of the pure substance (To) and that of the sample (Tm) were obtained and the sample purity was determined using the van't Hoff equation. A heat correction to linearize the van't Hoff plot was carried out to the negative range, because the decrease of the heat of fusion of the melt fraction with an decrease in the enthalpy of the eutectic mixture at the first heating was excluded. The purity measured by the DSC method can be determined to be fully reliable up to the purities of 95 mo1%.
  • 宮澤 智之, 高畠 亨, 長谷川 稔
    1997 年 117 巻 2 号 p. 126-132
    発行日: 1997/02/25
    公開日: 2008/05/30
    ジャーナル フリー
    Novel pyrido[2, 3-b]pyrazine 1, 4-dioxide and pyrido[2, 3-b]pyrazine 1-oxide derivatives were synthesized from furazano[4, 5-b]pyridine 3-oxide and the enolic form of 1, 3-diketones or β-ketoesters catalyzed by silica gel or molecular sieves. Their antibacterial activities were evaluated. As the results of antibacterial screening tests in vitro, pyrido[2, 3-b]pyrazine 1, 4-dioxide derivatives revealed strong activities, but pyrido[2, 3-b]pyrazine 1-oxide derivatives revealed no activities.
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