YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
111 巻, 9 号
選択された号の論文の11件中1~11を表示しています
  • 岸田 有吉, 内藤 敦, 岩藤 誠吾, 寺原 昭, 辻田 代史雄
    1991 年 111 巻 9 号 p. 469-487
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    The attempts to find a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which catalyzes the rate limiting step of cholesterol biosynthesis were started from 1971. The first potent inhibitor, ML-236B (compactin), was found from the culture broth of Penicillium citrinum. Among many derivatives of ML-236B, pravastatin sodium (hereafter refer to pravastatin) was finally selected because of its potency and tissue selectivity. Since pravastatin has a hydroxyl group at 6β position in the skeleton of decaline of ML-236B, the microbial hydroxylation was adopted for the production of pravastatin. Streptomyces carbophilus was finally chosen as a potent converter with the formation of a lesser amount of by-products. For the sake of industrial production of pravastatin, many devices and improvements were performed for selecting high potent strains and for culturing conditions both with ML-236B and pravastatin. Pravastatin strongly inhibited the sterol synthesis in freshly isolated rat hepatocytes, but only weakly inhibited in the cells from nonhepatic tissues. This selective inhibition of pravastatin in sterol synthesis was further confirmed by ex vivo and in vivo experiments by using rats and mice. Pravastatin markedly reduced serum cholesterol levels in dogs, monkeys and rabbits, including Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Pravastatin showed the preventive effect on the development of coronary atherosclerosis and xanthoma in young WHHL rabbits in consequence of maintaining the serum cholesterol levels low. In the clinical trials, pravastatin significantly reduced serum cholesterol and low density lipoprotein cholesterol levels, whereas inversely increased high density lipoprotein cholesterol levels.
  • 工藤 一郎
    1991 年 111 巻 9 号 p. 488-498
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    Phospholipase A2 hydrolyzes the ester linkage at sn-2 of glycerophospholipids and is thought to function as a key enzyme in generation of variety of bioactive mediators, such as prostaglandins and platelet-activating factor. In the present review, recent studies on two kinds of cellular phospholipases A2, 14kDa group II phospholipase A2 and arachidonate-preferentially hydrolyzing phospholipase A2, will be summarized.
  • 野田 敦子, 野田 浩司, 今村 孝史, 小野 行雄, 森田 美華, 甲斐 麻美子, 嶺 佐知子, 後藤 茂
    1991 年 111 巻 9 号 p. 499-503
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    Pentanthrene type heterocyclic compounds, which contain oxazole, isoxazole, oxadiazole, thiazole, isothiazole, thiadiazole or pyrrole ring as C-ring, and naphthalene, quinoline, isoquinoline or quinoxaline ring as A·B-ring, were prepared, and their monoamine oxidase (MAO) inhibitory activities were examined. As expected from our previous investigation on the structure-activity relationship of this series, most of them showed strong inhibitory potency to both MAO-A and MAO-B. However, a few indicated highly selective inhibition for either of MAO subtypes.
  • 生本 武, 佐々木 重夫, 難波 久子, 遠山 良介, 守時 英喜, 毛利 威徳
    1991 年 111 巻 9 号 p. 504-509
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    Tochukaso is a Chinese traditional medicine composed of a fruit body of Cordyceps sinensis and its parasitic host larva. Tochukaso (C. sinensis) and the cultured mycelia of five species of Cordyceps and four species of Isaria were each extracted with hot water and examined for the inotropic effect on guinea-pig right atrium in vitro system. The extracts from C. militaris and I. felina showed a negative inotropic effect to approximately the same extent as that from Tochukaso. These three extracts also showed inhibitory action on twitch response of guinea-pig ileum and aggregation of human blood platelet. It is suggested that these activities are ascribed to the combination of adenosine, 5'-adenosine monophosphate and several other nucleic acid-related compounds, all of which have been shown to be present in the extracts.
  • [りゅう] 紅星, 足立 伊佐雄, 堀越 勇, 上野 雅晴
    1991 年 111 巻 9 号 p. 510-514
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    A soybean oil emulsion was prepared by using milk fat globule membrane (MFGM) materials as an emulsifier. Its stability and effect on the intestinal absorption of vitamin D3, amphotericin B and kanamycin were studied. The MFGM emulsion was as highly stable as a Tween 80 emulsion. When the MFGM emulsion was sonicated with ultrasonic disrupter, the emulsion became more stable. Quantification of vitamin D3 in the intestinal lymph indicated that the MFGM emulsion enhanced lymphatic absorption of vitamin D3. The recovered percentage of vitamin D3 emulsified with MFGM in the lymph was 1.4 times that by Tween 80, and 2.5 times that of oil-in-water suspension. Statistically significant difference was found among them (p<0.05). The volumes of an oil phase in the emulsion affected the absorption of vitamin D3. The recovered percentage of vitamin D3 from the lymph increased with reducing the volume of the oil phase. Sonication of the emulsion did not affect the intestinal drug absorption. Furthermore, the MFGM emulsion had no effect on the intestinal absorption of amphotericin B and kanamycin.
  • 孕石 愛雄, 北沢 義夫, 坂井 学, 片岡 捷夫
    1991 年 111 巻 9 号 p. 515-523
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    The purpose of this study is to develop a new granulation method by using a fluidizedbed granulator, which requires a nucleus with a low melting point as a binder. This method was named as fluidized melt-granulation. The technique is very simple and useful. In this paper, the granulation mechanism and the effect of the physico-chemical properties of raw materials on the growth of the granules were investigated. The results were as follows : (1) The mixture of the nucleus and the other powder particles was heated up to the melting point of the nucleus by hot inlet air, immediately resulting in the generation of the adhesion of the powders on the melted nucleus. The granules grew as the melted material immersed into the void space among the adhered particles. (2) The lower the viscosity of the melted nucleus was, the faster the granule grew. (3) The shape and the size of the nucleus affected those of the products. (4) The optimum mixing ratio between the nucleus and the granulated materials existed and it depended on the ration between the surface areas of these materials.
  • 松崎 豊, 松崎 珠絵, 竹田 秀一, 小口 幸子, 池谷 幸信, 三橋 博, 佐々木 博美, 油田 正樹, 細谷 英吉, 尾山 力
    1991 年 111 巻 9 号 p. 524-530
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    Gomisin A (TJN-101) is one of the lignan components isolated from Schisandra Fruits and expected to have some efficacies in clinical treatment of hepatitis. The serum concentrations of TJN-101 and Met. B, which was identified as a demethylenated substance and one of the major metabolites of TJN-101 in rats, were investigated. After intravenous administration at doses of 1.6, 4.0 and 10 mg/kg of body weight, the serum concentration of TJN-101 decreased biphasically, and the terminal elimination half-life at each dose was about 70 min. Dose-dependency was observed for the area under the concentration-time curve (AUC). On the other hand, the serum concentration of TJN-101 increased rapidly and reached maximum within 15 to 30 min when administared orally. This result was supported by the in situ roop method. The Cmax and the AUC values were not exactly dose-dependent, but the values increased with a dose-up of TJN-101. The biotransformation of TJN-101 to Met. B, was very rapid in both intravenous and oral administrations. The AUC value of Met. B after oral administration of TJN-101 at a dose of 1.6 mg/kg was relatively larger than any other dosages. It suggested that TJN-101 was extensively underwent the first pass effect in rats. More than 80% of TJN-101 was bound with rat serum protein in vitro and in vivo. Therefore, it seems to be necessary to pay attention when it was administered concurrently with high protein binding drugs.
  • 松崎 豊, 松崎 珠絵, 小野 裕正, 小口 幸子, 竹田 秀一, 竹田 茂文, 布野 秀二, 油田 正樹, 細谷 英吉, 尾山 力
    1991 年 111 巻 9 号 p. 531-537
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    The absorption and excretion of gomisin A (TJN-101) in rats whose livers were injured by carbon tetrachloride (CCl4) were investigated. After intravenous administration of TJN-101 at a dose of 5 mg/kg, the terminal elimination half-life was 1.5 h in the CCl4-treated rats, which was two times that in normal rats. The mean area under the blood concentration-time curve (AUC) value of TJN-101 in the CCl4-treated rats was twice that in normal rats, and this difference was significant (p<0.05). Therefore, the total body clearance of TJN-101 in the CCl4-treated rats decreased less than half of that in normal rats. Similar results were observed when it was administered orally. In the CCl4-treated rats, the serum concentration of Met. B, which was identified as a demethylenated substance and one of major metabolites, tended to decrease more than that in normal rats. On the other hand, the cumulative biliary excretion ratio of TJN-101 in 24 h after dosing in the CCl4-treated rats was 2.5 times that in normal rats. The excretion rate of Met. B in the bile in the CCl4-treated rats tended to be delayed. However, the quantitative variance of biliary excretion of Met. B was not found in both groups. The urinary excretion of TJN-101 or Met. B in 72 h after dosing in the CCl4-treated rats was lower than that in normal rats. Similar results were also observed in excretion in the feces. It was speculated that these results were originated from suppression of the enzyme activity in the oxidative drug metabolism following the decrease of cytochrome P-450 induced by treatment with CCl4 and depression of re-absorption ratio in entero-hepatic circulation by hepatic failure. Consequently, it was demonstrated that the metabolic fate of TJN-101 was more extensively different in the CCl4-treated rats than in normal ones.
  • 田中 利明, 目鳥 幸一, 峯尾 哲, 広谷 正男, 古谷 力, 松本 仁, 佐藤 利夫, 小林 茂
    1991 年 111 巻 9 号 p. 538-541
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    A hot aqueous extract of Coptidis Rhizoma had an inhibitory effect on the bacterial collagenase from Clostridium histolyticum. Active principles were isolated by silica gel column chromatography from the CHCl8 extract. Consequently, two inhibitors obtained were identified with the chloride of berberine and coptisine. The concentrations of the berberine and coptisine in the assay mixture to give 50% inhibition (IC50) were 0.73 mM and 0.16 mM, respectively. The type of inhibition by coptisine chloride was shown to be a mixture type from Lineweaver-Burk plots. Tetrahydroberberine, a reduction product of berberine chloride, had no inhibitory effect. This result suggests that the quaternary nitrogen of the alkaloids plays an important role in inhibitory activity.
  • 大庭 美保子, 中村 淳, 松岡 昌弘
    1991 年 111 巻 9 号 p. 542-545
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    Typical 11 ultraviolet (UV) absorbers in cosmetic products were separated and determined by high performance liquid chromatography. The recommended conditions for the analysis were as follows : column, 4.6 mm i.d.×250 mm, Capcell Pak C18 SG (5μm) ; detector, UV spectrophotometer (280 nm) ; column temperature, 40°C ; mobile phase, H2O-CH3OH (15 : 85 v/v) containing 3 mM stearyltrimethyl ammonium chloride ; flow rate, 1.0 ml/min. In the case of the products containing 2-ethylhexyl p-methoxycinnamate (OMC) and /or 4-tert-butyl-4'-methoxydibenzoylmethane (BMD), it was necessary to use H2O-1, 4-dioxane (34 : 66 v/v) containing 6 mM stearyltrimethyl ammonium chloride as the mobile phase in order to separate OMC and BMD. Anthracene and 9, 10-dimethylanthracene were used as an internal standard for the H2O-CH3OH mobile phase and the H2O-1, 4-dioxane mobile phase, respectively. Calibration curves were linear within a range of 50-150μg/ml for the 11 UV absorbers. Recoveries and reproducibilities of the method were satisfactory. By using this method, typical UV absorbers in several commercial cosmetic products such as lip creams, sun oils, lotions and emulsions were able to be rapidly determined without any interference.
  • 石光 進, 藤本 貞毅, 竹原 潤, 山本 みやび, 小原 晃
    1991 年 111 巻 9 号 p. 546-550
    発行日: 1991/09/25
    公開日: 2008/05/30
    ジャーナル フリー
    The effect of copper on the concentrations of o- and m-tyrosines in the serum of guinea pigs was studied in vivo. When guinea pigs were fed the normal diet and 0.1% CuSO4 solution as a drinking water for 13 d, the concentrations of o-and m-tyrosines in the serum increased more significantly than that of guinea pigs fed normal diet and water without copper. Phenylalanine hydroxylase in the liver and kidney, and tyrosine hydroxylase in the brain and adrenal were not activated by the administration of copper to guinea pigs. The administration of copper caused an abnormal accumulation of copper in the liver, but not in the kidney, adrenal and brain, and significantly depressed the ascorbic acid content in various organs including the liver, kidney, brain and adrenal. The results obtained suggest that o-and m-tyrosines may be also formed nonenzymatically in vivo, in addition to the formation by the participation of enzymes such as phenylalanine and tyrosine hydroxylases.
feedback
Top