著者

西川 洋子 福本 紘一 鐵見 雅弘 形井 雅昭 廻 治雄

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.109, no.5, pp.340-343, 1989-05-25

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The grayanotoxin III (GTX III) was given intraperitoneally to rats at a dose of 0.8 or 2.8 mg/kg. To study the effects of GTX III on rats, biological tests in serum for functions of liver and kidney and their pathological observation were performed 1 h after the administration. Using analysis of variance, multiple comparison and correlation on biological parameters, activities of glutamic-pyruvic transaminase (GPT), guanase and leucine aminopeptidase and concentrations of total protein, albumin, creatinine, uric acid and K increased significantly. These parameters showed dose-effect relations with GTX III. Though GPT and free fatty acid increased significantly, dose-effect relations were not shown. The activity of choline esterase and the concentrations of bilirubin, urea-N, lipoperoxide, cholesterol, triglycerides, Na and Cl were not significantly different. Pathological changes were not observed in the liver and kidney of rats. These results show that GTX III may affect the functions of liver and kidney in rats.

著者

住谷 賢治 馬場 泰行 猪股 伸一 豊岡 秀訓 幸田 幸直

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)

巻号頁・発行日

vol.120, no.7, pp.652-656, 2000-07-01

参考文献数

17

被引用文献数

8

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Orally-disintegrating tablets of clonidine hydrochloride, an α_2-adrenergic agonist, were prepared by the method of drying an aqueous suspension. The suspension was prepared using powdered lactose, and the composition ratio was 2 : 1 (powdered lactose : 0.048% clonidine hydrochloride solution). The suspension was dried under 4±1℃(72±15% R.H.). We obtained tablets containing clonidine hydrochloride (40μg/tablet). Physical properties of the tablets were as follows : hardness was 4.0 kgf, and disintegration time was 41.7 s (in vitro). In the clinical use, 8 patients, aged 1-2 year and weighing 9-11 kg, received approximately 4μg/kg body weight as clonidine hydrochloride. The tablet was administered 90 min before entering the operating room. All patients were willing to accept the tablet. The quality of separation from parents, sedation and a mask acceptance were excellent on all patients. These results suggest that the orally-disintegrating tablet of clonidine hydrochloride was useful in a clinical situation for the preanesthetic medication of pediatric patients aged 1-2 year.

著者

才川 勇 桃井 海秀 酒井 広志 高下 寛 大橋 俊則 南 尚 山本 芳子 福岡 義和

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.99, no.12, pp.p1207-1218, 1979-12

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The stability, degradation pattern and structure of degradation products of sodium 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1551) in aqueous solution were investigated. T-1551 was kept in various solutions in pH and μ=0.5 at 35°, its degradation was followed by HPLC. T-1551 was stable at the range of pH 4.0-7.0,slightly unstable at acid and markedly unstable at alkaline. It was confirmed that in alkaline solution, 7-[D (-)-α-[3-[2-(N-ethyl-N-oxaloamino)-ethyl] ureido]-α-(4-hydroxyphenyl) acetamido]-3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid (T-1551A) was produced, and that in acidic solution, 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxy-methyl-3-cephem-4-carboxylic acid γ-lactone (T-1551B), 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid (T-1551C), 5-mercapto-1-methyl-1H-tetrazole (T-1551F), 2-[2-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-2-(4-hydroxyphenyl) acetamido]-2-[1,2,5,7-tetrahydro-7-oxo-4H-furo [3,4-d] [1,3] thiazin-2-yl] acetic acid (T-1551G), 2-[α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamidomethyl]-2,3-dihydro-5-hydroxy-methyl-6H-thiazine-4-carboxylic acid γ-lactone (T-1551H) and N-formylmethyl-D-(-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamide (T-1551D) were produced, respectively.

著者

Megan G. Marks Jiandong Shi Michael O. Fry Zili Xiao Michelle Trzyna Vedavalli Pokala Michael A. Ihnat Pui-Kai Li

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.5, pp.597-604, 2002 (Released:2002-05-10)

参考文献数

72

被引用文献数

42 52 68

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Angiogenesis, in particular anti-angiogenesis, is an area of particular therapeutic interest in cancer treatment. Several anti-angiogenic agents are in the final stages of clinical trials. One of these agents, thalidomide, best known for its teratogenic potential, is showing promise against several tumor types. Thalidomide has been shown previously to require bio-activation to exert its anti-angiogenic effect in isolated blood vessels and endothelial cells. In this work, we confirmed these findings using the in utero chicken embryo chorioallantoic membrane (CAM) system. In particular, the anti-angiogenic effect of thalidomide is significantly enhanced by activation by human but not by rat liver microsomes. We also showed in the CAM assay that hydroxylation of thalidomide at either the 1′- or 5-position retained anti-angiogenic activity whereas its hydroxylation at the 4-position led to an inactive compound. We further demonstrated that thalidomide shows weak anti-proliferative activity against MDA-MB-231 human breast cancer cells in culture. Thalidomide showed slightly more anti-proliferative activity, however, against the SH-SY5Y human neuroblastoma and human umbilical vein endothelial cell (HUVEC) types. Furthermore, incubation of thalidomide with human liver microsomes added no additional anti-proliferative effect in these cell types versus thalidomide given alone. Finally, we report that none of the thalidomide metabolites tested had any anti-proliferative effect against the breast or neuroblastoma cells, but do possess appreciable anti-proliferative activity against the endothelial cells. In summary, this work suggests that hydroxylated thalidomide analogs based on putative metabolites of the drug possess significant anti-angiogenic activity and that exploring further derivatives of these as potential anti-angiogenic agents warrants further merit.

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.80, pp.463-474, 1888-10-06

著者

橋本 肯子 安田 高明 大澤 啓助

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.112, no.5, pp.327-331, 1992-05-25

被引用文献数

4

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A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of synephrine in oriental pharmaceutical decoctions containing Aurantii Nobilis Pericarpium. An ODS column and a mixture of water, acetonitrile, sodium dodecyl sulfate and phosphoric acid (65 : 35 : 0.5 : 0.1) as a mobile phase were used for the separation. Synephrine was eluted without interference by other co-existing components within 15 min.

著者

宗野 真和

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.123, no.8, pp.653-663, 2003-08-01

被引用文献数

2

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合成反応やその戦略において炭素-炭素結合の形成反応は重要な課題であり,数多くの反応が開発されてきた.ヨウ化サマリウム(SmI_2)は,温和な条件で使用できる一電子還元剤であり,官能基の単純な還元に始まり,ケチルオレフィンカップリング反応,さらにはこれらを複数組み合わせたタンデム型反応などその報告例も近年増加しつつある.原子としてのサマリウムは,適度な還元力を有すること,イオン半径が長いこと,配位数が大きいこと,ルイス酸性が強いこと,酸素との親和力が大きいことなどの特徴を有する.また,SmI_2の還元力はある種の補助溶媒あるいは金属触媒を添加することにより調節できることが報告されている.例えば,SmI_2のAg/AgNO_3対照電極に対する酸化電位は,-1.33Vであるのに対し,HMPAを4eq.まで添加することで-2.05Vまで増強することができる.また,ある種のケチル-ラジカルカップリング反応の反応速度は,NiI_2の添加により増大することが報告されている.一方,電気化学的な見地から,不飽和カルボニル化合物の半波電位(vs.SCE)は,対応する飽和のカルボニル化合物とともによく研究されている.例えば,2.45V(cyclohexanone)>2.25V(methyl ethyl ketone)>1.8V(propionaldehyde)>1.55V(2-cyclohexen-1-one)>1.5V(acrolein)>1.42V(methyl vinyl ketone)のように,ケトンよりもアルデヒドの方が,また飽和のものより不飽和カルボニル化合物の方が容易に還元され得ることが分かる.私は以上のことを勘案し,SmI_2の反応系に添加物を加えることでその還元力と性質を変化させ,さらに分子内カルボニル基の種類をうまく組み合わせれば生成するケチルラジカル中間体をコントロールでき,結果として位置及び立体選択的に炭素骨格が構築できるのではないかと考えた.そこで,まず双環性化合物であるヒドリンダン誘導体の合成法を確立し,本方法が一般的に効力があるかいなかを確かめ,ついでこれらの反応を利用して天然物合成へ適用することを目標に定めた.具体的には,SmI_2を用いた還元的なエノン-アルデヒドの6-Endo-Trig-型の分子内閉環反応により,各種の置換基を有するヒドリンダノンの構築を詳細に検討した.さらにこの反応で得られたヒドリンダノン中間体を用いて,菌類代謝産物であるcoronafacic acid (9)の全合成を完了した.これらの結果について,順次述べる.

著者

山田 敏広 山下 武彦 中村 正則 嶋村 浩 山口 東 高谷 昌弘

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.100, no.8, pp.p799-806, 1980-08

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In order to obtain more hydrophylic and more potent hemostatics, 2-semicarbazono-1,2-naphthoquinone analogs with or without sulfonic acid or its salts at 4,5,6,7 or 8 position (III and IV) and 4-semicarbazido-1,2-naphthoquinone analogs (V) were prepared and their hemostatic activities and acute toxicities were examined. Among these compounds, more hydrophilic 2-semicarbazono-1,2-naphthoquinone analogs with sulfonic acid group (IIIj and IIIr) as well as less hydrophilic 2-semicarbazono-1,2-naphthoquinones without sulfonic acid group (IVa and IVh) and 4-semicarbazido-1,2-naphthoquinone analogs (Ve) showed the activity comparable to that of 2-semicarbazono-1,2-naphthoquinone (II) or carbazochrome sodium sulfonate (I) in shortening the bleeding time.

著者

平塚 信夫 芝 紀代子 篠村 勝美 保崎 清人 長 裕子 長崎 綾乃 小林 静子

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.17, no.10, pp.1355-1357, 1994-10-15

被引用文献数

6 10

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We fractionated normal urinary proteins obtained from 40 healthy subjects using cellulose acetate membrane electrophoresis and stained them with Acid Violet 17. The electrophoretic patterns were classified into four groups. Each of groups I, II, III, IV had an albumin peak and 1,2,3,and 4 additional globulin peaks, respectively. Within-day variation study showed that the pattern was fundamentally specific to the individual, although some intermediate cases were observed. We were unable to determine which type was standard for normal subjects. However, the concentration of Tamm-Horsfall protein was speculated to be an important factor in determining the patterns. Group III showed significantly higher values than group I in urine albumin, total protein, and β-N-acetyl-D-glucosaminidase and this group was believed to include subjects in the subclinical stage of a glomerular disease. All specimens belonging to group IV showed an obvious fraction of α_1 globulin which is often found in urine specimens of patients with renal diseases of tubular origin or other pathological conditions.

著者

Rina Miyake Tomohiro Uchimura Xu Li Totaro Imasaka

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.61, no.1, pp.82-84, 2013-01-01 (Released:2013-01-08)

参考文献数

13

被引用文献数

2

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Fluorescence lifetime imaging microscopy (FLIM) was used to monitor the interaction between androgen receptor (AR) tagging of a green fluorescent protein (GFP) and the ligands in living cells. The fluorescence lifetime of the AR-GFP without ligands was ca. 3.1 ns, which was reduced to ca. 2.5 ns after treatment with agonist 5α-dihydrotestosterone. On the other hand, the fluorescence lifetime of AR-GFP was not changed after treatment with antagonist hydroxyflutamide. The reaction kinetics was simulated in the present study, and the obtained results indicated the possibility of the presence of an intermediate complex during the reaction. FLIM can be used to record the ratio of the AR as it reacts with an agonist, and, therefore, it is useful for acquiring information concerning the interaction between AR and ligands in living cells.

著者

外村 正治 南城 実 狩野 静雄

出版者

公益社団法人日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.12, no.2, pp.119-120, 1966-04-30

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For the purpose of comparing air pollution in urban and rural area by the automotive exhaust gas, Pb concentration in the hair of regional inhabitants was examined and the following results were obtained. 1. In the determination of Pb in hair, it was found that the amount was larger in female than in male. 2. As for the difference in Pb concentrations by regions, the average and maximum values were larger in inhabitants in Tokyo than those in rural areas. 3. As for the difference in Pb concentrations by occupations, the average and minimum values were larger in traffic policemen in Tokyo than in men of other occupations in the same city.

著者

中村 優 堀田 桂子 冨野 和子 原 周司

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.98, no.3, pp.382-385, 1978-03-25

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It was found that the total mercury content of human growing hair had a tendency to decrease with the lapse of time. Long hair samples obtained from 252 females and 64 males, which were cut off at their scalp ends, were cut into 5 cm segments. Each segment was washed, dried, weighed, and its total mercury content was measured with a Zeeman-effect mercury analyzer. Distributions of total mercury along length of hair showed various patterns but, generally, the mean values of mercury content of the corresponding segments decreased in the order of scalp ends to the tips of hairs, regardless of sex or age. In order to clarify whether mercury escaped from growing hair with the lapse of time or whether mercury contamination of human body was progressing, which resulted in the increase of mercury content in the hair, hair samples obtained from 4 fixed persons were treated as above and stored, and then new hair samples from the same persons were obtained after the hair grew 5 cm, and the mercury content of the stored and new hair samples was compared. Its results indicated that mercury escaped from the growing hair with the lapse of time. From these facts measurement of the total mercury content in human hair should be carried out with samples cut at the scalp end and of a definite length.

著者

赤木 勘三郎

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

no.285, pp.1056-1064, 1905-11-26

著者

Takami Kakuda

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.12, pp.1513-1518, 2002 (Released:2002-12-01)

参考文献数

61

被引用文献数

65 121 133

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The neuroprotective effects of theanine and catechins contained in green tea are discussed. Although the death of cultured rat cortical neurons was induced by the application of glutamic acid, this neuronal death was suppressed with exposure to theanine. The death of hippocampal CA1 pyramidal neurons caused by transient forebrain ischemia in the gerbil was inhibited with the ventricular preadministration of theanine. The neuronal death of the hippocampal CA3 region by kainate was also prevented by the administration of theanine. Theanine has a higher binding capacity for the AMPA/kainate receptors than for NMDA receptors, although the binding capacity in all cases is markedly less than that of glutamic acid. The results of the present study suggest that the mechanism of the neuroprotective effect of theanine is related not only to the glutamate receptor but also to other mechanisms such as the glutamate transporter, although further studies are needed. One of the onset mechanisms for arteriosclerosis, a major factor in ischemic cerebrovascular disease, is probably the oxidative alteration of low-density lipoprotein (LDL) by active oxygen species. The oxidative alterations of LDL were shown to be prevented by tea catechins. Scavenging of ·O2− was also exhibited by tea catechins. The neuroprotective effects of theanine and catechins contained in green tea are a focus of considerable attention, and further studies are warranted.

著者

松村 靖夫 喜多 紗斗美 森本 史郎 秋元 健吾 古谷 真優美 岡 直美 田中 隆治

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.7, pp.1016-1019, 1995-07-15

被引用文献数

18 93

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We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The animals were unilaterally nephrectomized, and then separated into a sham-operated group (sham group) and a DOCA-salt-treated group. The latter was further separated into a normal diet group (control group) and a sesamin-containing diet group (sesamin group). The systolic blood pressure of control group progressively increased in comparison with that of sham group. This DOCA-salt-induced hypertension was markedly suppressed by feeding a sesamin-containing diet. Systolic blood pressure after 5 weeks was 130.6±1.9mmHg in the sham group, 198.1±7.3mmHg in the control group and 152.5±8.4mmHg in the sesamin group, respectively. The treatment with DOCA and salt for 5 weeks significantly increased the weight of the left ventricle plus the septum. However, this increase was signiflcantly suppressed in the sesamin group. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, there were significant increases in wall thickness, wall area and the wall-to-lumen ratio in the control group, compared with the sham. Sesamin feeding ameliorated the development of DOCA-salt-induced vascular hypertrophy in both the aorta and mesenteric artery. These findings strongly suggest that sesamin is useful as a prophylactic treatment in the development of hypertension and cardiovascular hypertrophy.

著者

森田 岩男 国本 克俊 津田 正己 但田 信一 黄瀬 正博 木村 喜代史

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.10, pp.4144-4154, 1987-10-25

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A series of 1,4-dihydropyridine-5-cyclic phosphonate derivatives, designed as analogues of 1,4-dihydropyridine-3,5-dicarboxylate calcium antagonists, was synthesized and examined for antihypertensive activity. Several compounds were proved to have activities superior or comparable to that of nifedipine in lowering blood pressure in normotensive and spontaneously hypertensive rats (SHR). Among these compounds, methyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (31, DHP-218) was approximately 7 times more active than nifedipine in SHR and was selected for further development and clinical evaluation. The structure-activity relationships are discussed.

著者

森田 岩男 津田 正己 黄瀬 正博 杉山 信

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.3, pp.1139-1142, 1988-03-25

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Attempts were made to improve the synthesis of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218), a new calcium antagonist. 2-Acetonyl-2-oxo-1,3,2-dioxaphosphosphorinane (5a), the key intermediate, was prepared from the allenylphosphonate (2) via the enaminophosphonate (4) in a good yield. Subsequently, the Knoevenagel condensation using 5a and the imine (6a) gave the benzylideneacetonylphosphonate (7a) in a good yield without the use of the Horner-Emons reaction. This condensation also gave good results for other acetonylphopshonates. The final step gave DHP-218 in a good yield through a modified Hantzsch synthesis with the use of a dehydrating agent. The overall yield was increased from 1.7% to 22%.

著者

手塚 康弘

出版者

公益社団法人日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.34, no.2, pp.164-165, 1998-02-01

著者

長屋 寿雄

出版者

公益社団法人日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.42, no.8, pp.851-852, 2006-08-01

著者

小山 次郎

出版者

公益社団法人日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.24, no.2, pp.182-183, 1988-02-01