著者

王 誠明 太田 節子 篠田 雅人

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.109, no.12, pp.949-953, 1989-12-25 (Released:2008-05-30)

参考文献数

24

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The survival effect of mice irradiated with a lethal dose of X-ray was studied by use of 60 kinds of Chinese traditional medicines. Methanol extracts of these medicines were prepared, and then each extract injected intraperitoneally into male mice before or after whole-body irradiation. As a result of these studies, the survival effects with Ogi-kentyu-to, Simotu-to, Sessyoin, Zokumei-to and Boi-ogi-to were observed by intraperitoneal injection before irradiation. Of these effective methanol extracts, only Zokumei-to was shown to have a significant survival effect by intraperitoneal injection after irradiation.

著者

中山 祥嗣

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.6, pp.795-798, 2016 (Released:2016-06-01)

参考文献数

1

被引用文献数

1

---

The Japan Ministry of the Environment is conducting a large-scale birth cohort study called the Japan Environment and Children's Study (JECS), which involves 100000 mother-child pairs. Mothers are enrolled during pregnancy, and their children are followed up and studied until they reach the age of 13 years. The JECS started recruiting mothers in January 2011 and completed the registration of more than 103000 mothers in March 2014. The National Institute for Environmental Studies takes the lead in the study programming and implementation in cooperation with the National Centre for Child Health and Development and 15 Regional Centres that reach out to the study participants. In the study, the effects of environmental factors on children's health and development are investigated. The environment in this study is defined not only as air, soil, water, and indoor environments but also as various chemical substances, physical conditions, socioeconomic factors, psychological conditions, lifestyles and community situations. Mothers' and children's exposures to these environmental factors are measured through chemical analyses of biospecimens collected during pregnancy and after birth, questionnaires and computer modelling. The homes of the randomly selected participants (5000) are visited to measure the concentrations of volatile organic compounds, nitrogen and sulphuric oxides and particulate matter. Vacuum dust samples are also collected for chemical analysis. All these data will be combined with the information collected by the dwelling unit observation to assess the exposure of children aged 1.5 and 3 years.

著者

高田 善之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.80, no.11, pp.1640-1641, 1960-11-25 (Released:2010-02-19)

参考文献数

3

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Application of alkaline hydrogen peroxide to sodium 2-cyanoethanesulfonate, obtained by reaction of acrylonitrile and sodium hydrogensulfite, afforded sodium 2-carbamoylethanesulfonate. Taurine (2-aminoethanesulfonic acid) was obtained in a comparatively good yield of 80-85% by reaction of the foregoing sulfonate and alkaline sodium hypochlorite.

著者

藤田 直

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.3, pp.203-218, 2002 (Released:2003-02-18)

参考文献数

60

被引用文献数

21 40

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It is well known that biomembranes and subcellular organelles are susceptible to lipid peroxidation. There is a steadily increasing body of evidence indicating that lipid peroxidation is involved in basic deteriorative mechanisms, e.g., membrane damage, enzyme damage, and nucleic acid mutagenicity. The formation of lipid peroxides can be induced by enzymatic or nonenzymatic peroxidation in the presence of oxygen. The mechanisms of formation and removal of reactive oxygen species, lipid peroxides, and free radicals in biological systems are briefly reviewed. In recent years, there has been renewed interest in the role played by lipid peroxidation in many disease states. Xanthine oxidase has been shown to generate reactive oxygen species, superoxide (O2−·), and hydrogen peroxide (H2O2) that are involved in the peroxidative damage to cells that occurs in ischemia-reperfusion injury. During ischemia, this enzyme is induced from xanthine dehydrogenase. We have shown that peroxynitrite (a reactive nitrogen species) has the potential to convert xanthine dehydrogenase to oxidase. The following biological effects of lipid peroxidation were found: a) the lipid peroxidation induced by ascorbic acid and Fe2+ affects the membrane transport in the kidney cortex and the cyclooxygenase activity in the kidney medulla, and b) the hydroperoxy adducts of linoleic acid and eicosapentaenoic acid inhibit the cyclooxygenase activity in platelets. The balance between the formation and removal of lipid peroxides determines the peroxide level in cells. This balance can be disturbed if cellular defenses are decreased or if there is a significant increase in peroxidative reactions. Once lipid peroxidation is initiated, the reactive intermediate formed induces cell damage.

著者

石黒 正路 西原 達郎 田中 里枝

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.121, no.12, pp.915-927, 2001-12-01 (Released:2002-09-27)

参考文献数

33

被引用文献数

5 8

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An orally active penem antibiotic, Farom (generic name: faropenem), was designed by the conformational analysis of active and inactive penem derivatives. Faropenem showed potent activity against a wide variety of bacteria including extended-spectrum β-lactamase (ESBL)-producing ones. The mechanism of the stability against ESBL was elucidated by modeling the Michaelis complex of faropenem and Toho-1, an ESBL. Modeling of a complex of faropenem at the active site of a penicillin-binding protein 2 (PBP2) model suggested the characteristic affinity for faropenem with PBP2 of Escherichia coli. Faropenem has been totally synthesized from (R)-1,3-butanediol. The synthetic intermediate, a 3-hydroxyethyl-4-acetoxyazetidinone derivative, was efficiently prepared by the 2+2 coupling of a optically active vinyl-sulfide derivative and chlorosulfonyl isocyanate, followed by the substitution of the acetoxy group for the thiophenyl group at the C-4 position.

著者

小松 生明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.2, pp.329-335, 2016-02-01 (Released:2016-02-01)

参考文献数

34

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Morphine with its potent analgesic property has been widely used for the treatment of various types of pain. However, the intrathecal (i.t.) administration of morphine at doses far higher than those required for antinociception exhibited nociceptive-related behaviors consisting of scratching, biting and licking, hyperalgesia, and allodynia in mice. Morphine-3-glucuronide (M3G), one of the major metabolites of morphine, has been found to evoke nociceptive behaviors similar to those after high-dose i.t. morphine. It is plausible that M3G may be responsible for nociception seen after high-dose i.t. morphine treatment. This article reviews the potential mechanism of spinally mediated nociceptive behaviors evoked by i.t. M3G in mice. We discuss the possible presynaptic release of nociceptive neurotransmitters/neuromodulators such as substance P, glutamate, dynorphin, and Leu-enkephalin in the primary afferent fibers following i.t. M3G administration. It is possible to speculate that i.t. M3G could indirectly activate NK1, NMDA, and δ2-opioid receptors that lead to the release of nitric oxide (NO) in the dorsal spinal cord. The major function of NO is the production of cGMP and the activation of protein kinase G (PKG). The NO-cGMP-PKG pathway plays an important role in M3G-induced nociceptive behavior. The phosphorylation of extracellular signal-related kinase (ERK) in the dorsal spinal cord was also evoked via the NO-cGMP-PKG pathway through the activation of δ2-opioid, NK1, and NMDA receptors, contributing to M3G-induced nociceptive behaviors. The demonstration of a neural mechanism underlying M3G-induced nociception provides a pharmacological basis for improved pain management with morphine at high doses.

著者

野口 照久 橋本 喜信 小坂 璋吾 菊池 正義 宮崎 幸信 先本 礼次 加治 有恒

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.88, no.3, pp.344-352, 1968-03-25 (Released:2008-05-30)

参考文献数

21

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Some observations were made on the anti-trichophyton action of 2-naphthyl N-methyl-N-arylthiocarbamate (A). In vitro antifungal activity decreased slightly when the thiocarbamate was changed to carbamate, and a marked lowering in the in vitro effect was observed. The antifungal activity disappeared entirely when the thiocarbamate was changed to dithiocarbamate and thiolcarbamate. When the aryl group in A is a naphthyl, antifungal activity is present only when 1-naphthyl is present and other three combinations are entirely ineffective. When the aryl is a substituted phenyl, compounds having methyl, methoxyl, or halogens, those with the Hammet constant in the range of +0.23 to -0.27, have marked antitrichophyton activity in vivo, but those with nitro, formyl, carboxyl, sulfonamido hydroxyl, or dimethylamino group show marked decrease in the effect. The series of compounds having the A type will henceforth be designated as naphthiomates.

著者

野口 照久 小坂 璋吾 橋本 喜信 菊池 正義 宮崎 幸信 加治 有恒

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.88, no.3, pp.353-358, 1968-03-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

1 2

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Examinations were made on the effect of oral administration of 2-naphthyl N-methyl-N-arylthiocarbamates (naphthiomates), an effective antimicotic agent for external use, against experimental trichophytosis. Finely powdered 2-naphthyl N-methyl-N-(m-tolyl)-thiocarbamate (naphthiomate-T) and 2-naphthyl N-methyl-N-(1-naphthyl) thiocarbamate (naphthiomate-N) showed an effect comparable to griseofulvin in about four-fold dose of the latter. In vivo metabolism of naphthiomate-T was examined in guinea pigs and rabbits, and it was found that the majority is excreted in the feces without decomposition, and little is absorbed through the intestinal tract. N-Methyl-m-toluidine and β-naphthol were detected from urine, feces, and blood as the metabolites.

著者

青山 豊彦 塩入 孝之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.115, no.6, pp.446-459, 1995-06-25 (Released:2008-05-30)

参考文献数

22

被引用文献数

3 5

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Tilivalline (1a), a metabolite isolated from Klebsiella pneumoniae var. oxytoca, belongs to a group of pyrrolo [2, 1-c] [1, 4] benzodiazepines, a characteristic skeleton of anthramycin-type antitumor antibiotics. We have accomplished a completely stereoselective, efficient and convenient synthesis of 1a utilizing a new Mannich type intramolecular cyclization as a key step. Further, a computational chemical analysis clarified the effect of zinc chloride on the high stereoselectivity in the tilivalline synthesis. To aim both the extension of the scope of the new Mannich type intramolecular cyclization and the studies on the structure-biological activity relationship, we further extended the method to the synthesis of tilivalline derivatives and 2-(3'-indolyl)-1, 4-benzodiazepines (50). Investigation on the cytotoxicity of 1a and its analogs has revealed that 1a shows the strong cytotoxicity toward mouse leukemia L 1210 cells and the replacement of the indole function of 1a with cyano one increases the cytotoxicity of 1a about 100 times (IC50=0.05 μg/ml).

著者

塩入 孝之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.113, no.11, pp.760-780, 1993-11-25 (Released:2008-05-30)

参考文献数

69

被引用文献数

1

---

Recent studies on the new methods and new reagents in organic synthesis developed by our laboratories have been reviewed. Their application to the synthesis of biologically intriguing natural products has been also described. Dolastatin 10 (1), a potent antitumor peptide of marine origin, has been efficiently synthesized by use of diethyl phosphorocyanidate (DEPC), diphenyl phosphorazidate (DPPA) and (+)-2-hydroxy-3-pinanone ((+)-HyPN). Mugineic acid (27), a typical phytosiderophore from barley, has been synthesized using a phenyl group as a carboxyl synthon. The method is quite efficient to produce mugineic acid on a large scale. Tilivalline (50), isolated from Klebsiella pneumoniae var. oxytoca, has been synthesized by use of DPPA as an +NH2 synthon and DEPC as a coupling reagent. The new Mannich type reaction has been explored to construct the pyrrolo [2.1-c] [1.4] benzodiazepine skeleton. The chiral phase transfer catalyst (65a) based on cinchonine has been utilized for the asymmetric hydroxylation of the α-tetralone derivatives (63). The first synthesis of the chiral ammonium fluoride (71) has been achieved, and its use for the silicon-based asymmetric aldol reaction has been accomplished. Trimethylsilyldiazomethane (TMSCHN2) has been developed as a stable and safe substitute for hazardous diazomethane. As a C1-unit introducing reagent, TMSCHN2 and its lithium salt mostly realize the reactions similar to those carried out with diazomethane. On the other hand, they generally behave as a [C-N-N] azole synthon in an analogous but not as the same way as diazomethane. Using the lithium salt of TMSCHN2, new methods for the preparation of alkynes and pyrroles have been developed.

著者

末宗 洋

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.112, no.7, pp.432-446, 1992-07-25 (Released:2008-05-30)

参考文献数

42

被引用文献数

4 6

---

The use of biocatalysts for the preparation of new chiral synthons has provided a novel synthetic route to the useful natural products. A method for the preparation of chiral carbocyclic alcohols has been also developed by utilizing the Pseudomonas fluorescens lipase (PFL)-catalyzed enantioselective hydrolysis. The above-mentioned alcohols have been found to be effective as chiral auxiliaries for asymmetric reactions.

著者

市川 聡

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.10, pp.1403-1430, 2008-10-01 (Released:2008-10-01)

参考文献数

149

被引用文献数

2 4

---

Nucleosides and nucleotides are one of the most important elements for cells by the fact that they are components of DNAs and RNAs. In addition, they play important roles in most fundamental cellular metabolic pathways such as energy donors, second messengers, and cofactors for various enzymes. Therefore, there exists a rich source in drug discovery targeting nucleosides and nucleotides. In order to utilize nucleosides and nucleic acids on the drug development, it is very important to develop reactions and methods, by which the highly coordinating and labile nucleoside intermediates can be used. With these in mind, we have been working on synthetic nucleoside and nucleic acid chemistry. First, branched sugar nucleoside derivatives, which are potential antitumor agents, have been synthesized utilizing samarium diiodide (SmI2) mediated Reformatsky reaction or aldol reaction. 3′-β-Carbamoylmethylcytidine (CAMC) was found to exhibit potent cytotoxicity against various human tumor cell lines. Synthetic methodology of the caprazamycins, which are promising antibacterial nucleoside natural products, was also developed by the strategy including β-selective ribosylation without using a neighboring group participation. Our synthetic route provided a range of key analogues with partial structures to define the pharmacophore. Simplification of the caprazamycins was further pursued to develop diketopiperazine analogs. Medicinal chemistry of oligodeoxynucleotides has been conducted. Thus, novel triazole-linked dumbbell oligodeoxynucleotides and modular bent oligodeoxynucleotides were synthesized. They exhibit excellent binding affinity to NF-κB or HMGB1 A-box protein, which are important therapeutic targets. Therefore, the results obtained conclusively demonstrated these oligodeoxynucleotides could be proposed as powerful decoy molecules.

著者

黒田 耕司 横山 照由 梅田 常雄 喜多 良昭 小西 明 黒田 勤

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.7, pp.745-751, 1979-07-25 (Released:2008-05-30)

参考文献数

7

被引用文献数

2 2

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Physicochemical properties of the polymorphs and hydrate of 6-mercaptopurine were investigated. Its crystal habits were slightly changed and form I-TX was obtained by the addition of 6-thioxanthine and/or 2, 6-dithioxanthine and subsequent recrystallization. It was found that when Form I-TX was heated at 240°, this form transformed to Form III which was found to have a solubility about 6-7 times that of Form I. The mutual transition of 6-mercaptopurine polymorphs and hydrate under various conditions of heating and suspending in water was also studied. The transition temperature and the heat of transition between Form I-TX and Form II-TXhyd were determined to be 127°and 2.15 kcal/mol, respectively, by the solubility measurement. It was expected that if the transition of Form III could be suppressed, more bioavailable preparation of 6-mercaptopurine would be obtained.

著者

酒井 浄

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.28, no.6, 1992

著者

大津 隆行 的場 啓子 菊地 茂行 平尾 一郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.75, no.4, pp.368-371, 1955-04-25 (Released:2010-02-19)

参考文献数

8

被引用文献数

3

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Polyvinylpyrrolidone, used as the substitute plasma, is said to be effective when the molecular weight is around 30, 000 to 50, 000, and the inclusion of lower or higher molecules is thought to give adverse effect as a substitute plasma. The polymer obtained by the polymerization of vinylpyrrolidone with hydrogen peroxide and ammonia catalyst was extracted with acetone at a room temperature and fractionated by reprecipitaton from aqueous solution with acetone, obtaining a distribution curve for molecular weights.On the other hand, distribution curve of molecular weights was also obtained by the same method from the polyvinylpyrrolidone marketed by the German Bayer and the two curves were found to be very similar. These results show that the extraction of low molecular polymers with a solvent like acetone is effective in obtaining polyvinylpyrrolidone of high homogeneity. Polyvinylpyrrolidone is known to take a coiled form in a solution that its viscositic characteristics in dilute aqueous solution were also examined and it was observed that the Huggins' viscosity constant, k', markedly changes with the degree of polymerization.

著者

兼松 顯

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.19, no.3, pp.245-248, 1983

著者

小林 直樹 岡本 康

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.39, no.8, pp.769-773, 2003

参考文献数

15

著者

小泉 裕久

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.52, no.3, pp.246-247, 2016

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キャベツ汁中から発見されたメチルメチオニンスルホニウムクロリド(MMSC)を配合した総合胃腸薬「キャベジンコーワ」は、1960年2月の発売から55年が経ち、現在では8代目となる「キャベジンコーワα」を販売するに至った。古くて新しい胃腸薬として、これからも生活者の皆さまの期待に応えていきたい。

著者

宮地 幸隆 下条 正子

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.30, no.7, pp.777-781, 1994

被引用文献数

1

著者

王子田 彰夫 高嶋 一平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.1, pp.3-7, 2016 (Released:2016-01-01)

参考文献数

7

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Fluorescence probes are now widely used as indispensable tools in many cell functional analyses. At present, the design of fluorescent probes largely depends on the limited numbers of established sensing mechanisms such as photo-induced electron transfer (PET), photo-induced charge transfer (PCT), and fluorescence resonance energy transfer (FRET). Although these mechanisms are versatile in metal ion sensing, introduction of a new sensing mechanism is highly desirable not only to design a more sophisticated probe with high selectivity and sensitivity but also to expand the diversity of the sensing targets to unveil biological phenomena. In this article, we report the design of dual emission fluorescent probes for metal ions based on a unique fluorescence-sensing mechanism. The fluorescent probes incorporating this sensing mechanism displayed a large emission red-shift on complexation with metal ions such as CdII and AgI. X-ray crystallography and theoretical computational calculations of the CdII and AgI complexes revealed that the emission shift was induced by non-coordination contact between the aromatic ring of fluorophore and the metal ion (arene-metal ion contact; AM-contact), which modulates the energy levels of molecular orbitals. The fluorescent probe was successfully applied to in cell ratiometric bioimaging of bioactive hydrogen sulfide (H2S). These successful applications highlight the usefulness of this sensing mechanism in biological fluorescence analysis.