著者

安宅 弘司 伊藤 雅文 柴田 高

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.125, no.12, pp.937-950, 2005-12-01

被引用文献数

2 5

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Wood creosote, the principal ingredient in Seirogan, has a long history as a known gastrointestinal microbicidal agent. When administered orally, the intraluminal concentration of wood creosote is not sufficiently high to achieve this microbicidal effect. Through further animal tests, we have shown that antimotility and antisecretory actions are the principal antidiarrheal effects of wood creosote. Wood creosote inhibits intestinal secretion induced by enterotoxins by blocking the Cl^- channel on the intestinal epithelium. Wood creosote also decreases intestinal motility accelerated by mechanical, chemical, or electrical stimulus by the inhibition of the Ca^<2+> influx into the smooth muscle cells. In this overview, the antimotility and antisecretory effects of wood creosote are compared with those of loperamide. Wood creosote was observed to inhibit stimulated colonic motility, but not normal jejunal motility. Loperamide inhibits normal jejunal motility, but not stimulated colonic motility. Both wood creosote and loperamide inhibit intestinal secretion accelerated by acetylcholine. Wood creosote was found to have greater antisecretory effects in the colon than loperamide. Based upon these findings, we conclude that the antidiarrheal effects of wood creosote are due to both antisecretory activity in the intestine and antimotility in the colon, but not due to the microbicidal activity as previously thought. Wood creosote was found to have no effects on normal intestinal activity. These conclusions are supported by the results of a recent clinical study comparing wood creosote and loperamide, which concluded that wood creosote was more efficacious in relieving abdominal pain and comparable to loperamide in relieving diarrhea.

著者

Tohru Sakai Miyuki Ohhata Misaki Fujii Sayaka Oda Yasuna Kusaka Miki Matsumoto Akiko Nakamoto Tomoyo Taki Mariko Nakamoto Emi Shuto

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.40, no.4, pp.391-395, 2017-04-01 (Released:2017-04-01)

参考文献数

27

被引用文献数

16

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Propolis is a bee product with various biological properties. C57BL/6 mice were fed a high-fat diet and treated with propolis for 14 weeks. Body weight in mice treated with 2% propolis was less than that in control mice from 3 weeks after the start of treatment until 14 weeks except for the 7th week. Mice treated with propolis showed significantly lower epididymal fat weight and subcutaneous fat weight. Infiltration of epididymal fat by macrophages and T cells was reduced in the propolis group. Supplementation of propolis increased feces weight and fat content in feces, suggesting that mechanisms of weight reduction by propolis partly include a laxative effect and inhibition of fat absorption.

著者

三橋 博 金子 光 佐々木 希吉

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.10, no.11, pp.1119-1122, 1962-11-25

---

It was shown that DL-phenylalanine [2-^<14>C] was incorporated into C-3 of two kinds of isoflavone, formononetin and genistein, by Trifolium pratense sp., in vivo. These results indicate that the aryl group undergoes a migration within the C_6-C-C-C fragment, and this observation agrees with Grisebach's experimental data.

著者

川口 安郎 中村 芳正 佐藤 俊幸 武田 節夫 丸中 照義 藤井 節郎

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

vol.98, no.4, pp.525-536, 1978

被引用文献数

8

---

After oral administration of 5-fluoro-1, 3-bis (tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1), the level of 5-fluoro-2, 4-pyrimidinedione (5-FU) was 5 to 7 times higher in the plasma and normal tissues and 8 to 12 times in tumor tissue than after administration of 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). Moreover, these levels were maintained longer than after administration of FT. In tumor tissue, the concentration of 5-FU was still as high as 1.42 &mu;g/g 12 hr after administration of FD-1. FD-1 was degraded to 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) by liver microsomal drug-metabolizing enzymes in vitro and to FT spontaneously. Subsequently, FT was converted enzymically to the active substance, 5-FU, and 3-FT changed to 5-FU spontaneously. Conversion of FD-1 to 5-FU via 3-FT was greater than via FT. It is concluded that a large amount of 5-FU formed after administration of FD-1 is formed via 3-FT. &gamma;-Hydroxybutyric acid was found to be formed in vivo and in vitro from the tetrahydrofuranyl group of FD-1.

著者

衣笠 豊 服部 安藏

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.485, pp.579-595, 1922-07-26

著者

新藤 恭司 安田 行寛 多比良 和基 三谷 鳴夫 神田 敦弘 赤沢 明

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.99, no.12, pp.1186-1200, 1979

被引用文献数

5

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The biological fate of 4-butyl-4-(&beta;-carboxypropionyl-oxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione (Suxibuzone, SB) was compared with that of phenylbutazone (PB) in rats, rabbits, beagle dogs and rhesus monkeys. The results obtained were as follows ; 1) When SB was administered orally, the main metabolites in the plasma were PB, oxyphenbutazone (Oxy-PB) and &gamma;-hydroxyphenylbutazone (&gamma;-Hydroxy-PB) in all species, though species differences were observed in the maximum plasma levels of the respective metabolites. Only in dogs and monkeys, was a small amount of SB detected in the plasma during the early time of dosing. 2) The metabolites and their maximum levels in plasma after the administration of SB were almost identical with those observed after the administration of PB. 3) After administration of SB, the main metabolites found in urine were PB, Oxy-PB, &gamma;-Hydroxy-PB and their conjugates in all species, while species differences were observed in the percent excreted. In the dogs and monkeys, urinary excretion as the form of SB and 4-hydroxymethylphenylbutazone (4-HM-PB) glucuronides was observed in small amount for 0-12 hours. 4) There were no significant differences in the metabolites and their excreted percent in urine between SB and PB administration. 5) Differences between male and female in maximum plasma levels of PB and &gamma;-Hydroxy-PB and in urinary excreted percent of &gamma;-Hydroxy-PB were observed only in rats. 6) Species differences were observed in esterase activity on SB in vitro. 7) SB was bound to the albumin fraction as in the case of PB, but its binding percent was about 1/2 lower than that of PB. 8) SB showed anti-edematous action on carrageenin-induced edema and its activity was almost similar to that of PB. Anti-edematous activity of Oxy-PB was weaker than that of SB and &gamma;-Hydroxy-PB had no effect on its action.

著者

酒井

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.208, pp.584-585, 1899-06-26

著者

今村 孝史 野田 敦子 柴田 重信 渡辺 繁紀 野田 浩司 小野 容子 後藤 茂 井上 善文

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.113, no.5, pp.400-405, 1993-05-25

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A series of pentanthrene type heterocyclic compounds were synthesized and evaluated for anxiolytic activities by three kinds of behavioral pharmacological tests. Several compounds showed anxiolytic activities. In particular, s-triazolo [3,4-a] phthalazine (Tri-P) and 3-propyl derivatives of Tri-P (PTP) showed remarkable activities, although the activities were slightly lower than those of diazepam. The results suggested that Tri-P or PTP is a useful lead compound for the development of the antianxietic agents. The relationship between the structure and anxiolytic activity, and the inducing mechanism of the activity was discussed.

著者

山本 経之

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.37, no.12, pp.1104-1108, 2001-12-01

著者

荒田 洋治

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.49, no.10, 2013-10-01

著者

Kiyofumi Inamoto

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.10, pp.987-996, 2013-10-01 (Released:2013-10-01)

参考文献数

70

被引用文献数

5 17

---

Herein, we describe our development of synthetic methods for heterocyclic compounds based on the palladium-catalyzed carbon–hydrogen bond (C–H) functionalization/intramolecular carbon–heteroatom (nitrogen or sulfur) bond formation process. By this C–H cyclization method, we efficiently prepared various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are typically good to high and good functional-group tolerance is observed for each process, thereby indicating that the method provides a novel, highly applicable synthetic route to the abovementioned biologically important heterocyclic frameworks. As an application of this approach, an auto-tandem-type, one-pot process involving the oxidative Heck reaction and subsequent C–H cyclization using cinnamamides and arylboronic acids as starting materials in the presence of a palladium catalyst was also developed for the rapid construction of the 2-quinolinone nucleus.

著者

Mitsuhiro Machitani Fuminori Sakurai Keisaku Wakabayashi Kosuke Nakatani Kazuo Takayama Masashi Tachibana Hiroyuki Mizuguchi

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.40, no.3, pp.272-277, 2017-03-01 (Released:2017-03-01)

参考文献数

25

被引用文献数

7

---

Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome engineering technology is a powerful tool for generation of cells and animals with engineered mutations in their genomes. In order to introduce the CRISPR/Cas9 system into target cells, nonviral and viral vectors are often used; however, such vectors trigger innate immune responses associated with production of type I interferons (IFNs). We have recently demonstrated that type I IFNs inhibit short-hairpin RNA-mediated gene silencing, which led us to hypothesize that type I IFNs may also inhibit CRISPR/Cas9-mediated genome mutagenesis. Here we investigated this hypothesis. A single-strand annealing assay using a reporter plasmid demonstrated that CRISPR/Cas9-mediated cleavage efficiencies of the target double-stranded DNA were significantly reduced by IFNα. A mismatch recognition nuclease-dependent genotyping assay also demonstrated that IFNα reduced insertion or deletion (indel) mutation levels by approximately half. Treatment with IFNα did not alter Cas9 protein expression levels, whereas the copy numbers of guide RNA (gRNA) were significantly reduced by IFNα stimulation. These results indicate that type I IFNs significantly reduce gRNA expression levels following introduction of the CRISPR/Cas9 system in the cells, leading to a reduction in the efficiencies of CRISPR/Cas9-mediated genome mutagenesis. Our findings provide important clues for the achievement of efficient genome engineering using the CRISPR/Cas9 system.

著者

Shigeo Yasuda Haruna Yokosawa Chisato Mukai

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.64, no.7, pp.805-810, 2016-07-01 (Released:2016-07-01)

参考文献数

28

被引用文献数

2 3

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Treatment of the allenylazetidine–alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)propane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C–C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved.

著者

室伏 良信 木村 美佐子 桑野 晴光 飯島 康輝 山崎 光郎 金子 正勝

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.10, pp.3760-3769, 1988-10-25

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Addition reactions of the C^<4′>-C^<5′> double bond of griseolic acid were investigated. C^<4′>-C^<5′>Dihydrogrisiolic acid was obtained by reduction of the adduct having halogen at the 4′-position.The ring juncture of the two five-membered rings of the C^<4′>-C^<5′> dihydro derivaticves was of all-"cis"configuration. Acetolysis of the protected dihydrogriseolic acid gave the corresponding 1′-acetoxy sugar derivative. Reaction of this sugar derivative with silylated bases gave guanine and uracil derivatives of the dihydrogriseolic acid. The cyclic nucleotide phosphodiesterase (PDE)-inhibitory activity of the C^<4′>-C^<5′> cis dihydrogriseolic acid derivative was weaker than that of griseolic acid.The uracil derivative of C^<4′>-C^<5′> cis dihydrogriseolic acid completely lost the inhibitory activity against both adenosine 3′, 5′-cyclic monophosphate (cAMP) and guanosine 3′, 5′-cyclic monophosphate (cGMP) PDE, whereas the guanine derivative showed reduced inhibitory activity against cAMP PDE, but retained its activity against cGMP PDE. It was also apparent that the C^<4′>-C^<5′>trans dihydro derivative which was obtained as a minor product from the same culture broth of griseolic acid had almost the same inhibitory activity as griseolic acid.

著者

Kazuki Ide Yohei Kawasaki Ryo Iketani Naohiko Masaki

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

pp.b16-00941, (Released:2017-02-17)

参考文献数

23

被引用文献数

2

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In this study, a nationwide database was used to identify the risk factors for treatment discontinuation due to adverse events during telaprevir, peginterferon, and ribavirin (T/PR) treatment, and estimate the increase in the occurrence of adverse events when patients have multiple risk factors at the same time. The risk factors were identified using univariate logistic regression analysis, and a Cochran–Armitage trend test was used to analyze the correlation between the number of risk factors and treatment discontinuation due to adverse events. Of the 25,989 individuals registered in the database, 1,668 (age, mean ± SD: 58.0 ± 9.9) were included in the study. Of these, 188 (11.27%) discontinued T/PR therapy due to adverse events. In the univariate logistic regression analysis, sex, age, AST level, and platelet count were found to significantly affect the incidence of T/PR treatment discontinuation (P < 0.05). Furthermore, the incidence of treatment discontinuation gradually increased from 4.6% to 27.2% as the number of risk factors increased from 0 to 4, and the Cochran–Armitage trend test showed a significant correlation (P < 0.001). In conclusion, this study not only revealed the risk factors for treatment discontinuation but also showed that patients with multiple risk factors are more likely to discontinue treatment due to adverse events compared to patients with fewer risk factors.

著者

Takashi Nakamura Yosuke Noma Yu Sakurai Hideyoshi Harashima

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.40, no.2, pp.234-237, 2017-02-01 (Released:2017-02-01)

参考文献数

12

被引用文献数

17

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Intravesical drug delivery by cationic liposomes (Cat-LPs) represents a potent nanotechnology for enhancing therapeutic effects against bladder disorders. However, preventing the aggregation of Cat-LPs in urine poses a significant barrier. We report on an examination of the effect of modifying liposomes with polyethylene glycol (PEG) lipids to prevent Cat-LPs from aggregating in human urine. Although Cat-LPs underwent significant aggregation in human urine, introducing 5 mol% of PEG2k lipid or 2 mol% of PEG5k lipid completely inhibited the aggregation of the Cat-LPs. When 2 mol% of PEG2k lipids were introduced, the lipid structures of 1,2-distearoly-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-distearoyl-sn-glycerol (DSG) greatly prevented aggregation compared with cholesterol. By contrast, when Cat-LPs, after incubation in urine, were exposed to bladder cancer cells, only introducing cholesteryl-PEG into the Cat-LPs showed a significant enhancement in cellular uptake. These results offer the potential for incorporating cholesteryl-PEG into Cat-LPs for achieving both stability in urine and effective cellular uptake.

著者

Kengo Hanaya Kazuaki Matsumoto Yuta Yokoyama Junko Kizu Mitsuru Shoji Takeshi Sugai

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.65, no.2, pp.194-199, 2017-02-01 (Released:2017-02-01)

参考文献数

14

被引用文献数

1

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Linezolid (1) is an oxazolidinone antibiotic that is partially metabolized in vivo via ring cleavage of its morpholine moiety to mainly form two metabolites, PNU-142300 (2) and PNU-142586 (3). It is supposed that accumulation of 2 and 3 in patients with renal insufficiency may cause thrombocytopenia, one of the adverse effects of linezolid. However, the poor availability of 2 and 3 has hindered further investigation of the clinical significance of the accumulation of these metabolites. In this paper, we synthesized metabolites 2 and 3 via a common synthetic intermediate, 4; this will encourage further exploration of events related to these metabolites and lead to improved clinical use of linezolid.

著者

白石 忠義 亀山 啓司 今井 直博 堂本 剛史 勝見 郁男 渡辺 清

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.974-981, 1988-03-25

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A series of α-cyanocinnamamide derivatives was synthesized and evaluated for inhibitory activity against tyrosine-specific protein kinase using intact plasma membrane fractions from an epidermoid carcinoma cell line, A-431 cells. Among these compounds, several novel α-cyano-4-hydroxy-3,5-disubstituted cinnamamide derivatives, e.g., α-cyano-3-ethoxy-4-gtdrixt-5-phenyl-thiomethylcinnamamide (ST 638), showed potent inhibitory activity. The studies on the structure-activity relationship revealed that the presence of the hydroxy group at the 4 position and the double bond in the α-cyano-4-hydroxycinnamamide skeleton was important for potent inhibitory activity, and that the presence of hydrophobic groups at the 3 and 5 positions on the benzene ring also enhanced the inhibitory activity of α-cyano-4-hydroxycinnamamide derivatives.

著者

瀬尾 量 鶴岡 道雄 橋本 強 藤永 稔夫 小田切 優樹 上釜 兼人

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.31, no.1, pp.286-291, 1983-01-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

48 62

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Inclusion complex formations of spironolactone (SP) with three cyclodextrins (α-, β-, γ-CyDs) in aqueous solution and in the solid state were studied by the solubility method, by spectroscopic methods (UV, CD, IR) and by X-ray diffractometry, and their modes of interaction were assessed. The solid complexes of SP with β- and γ-CyDs were obtained in molar ratios of 1 : 2 and 2 : 3, respectively, and their dissolution, membrane permeation and oral absorption properties were examined. The rates of dissolution and permeation through a cellophane membrane in water were significantly increased by inclusion complexation (γ-CyD complex>β-CyD complex>SP alone), depending upon the solubility of the test samples. The serum levels of SP following oral administration of CyD complexes were found to be greater than those after administration of SP alone. The results indicated that the γ-CyD complex rather than β-CyD complex may have great utility as a faster dissolving form of SP able to produce higher serum levels.

著者

南 基泰 四方 恒生 長谷川 千晃 大江 千里 芦田 馨 杉野 守

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.115, no.10, pp.832-842, 1995-10-25

被引用文献数

6

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We studied that the morphological and histological characteristics, and the content (%DW) of saikosaponins on the root of Bupleurum falcatum cultivated in an Ebb & Flood system (E&F), a kind of soilless culture system, by both the direct sowing and the transplanting methods, and that effects of pinching on the root growth and the content (%DW) of saikosaponins in each part of root. Yield of root and content (%DW) of saikosaponins in each part of root, 8-months-old, cultivated in E&F by both methods were at the same level as that cultivated for the same period in soil conditoin by generally standard procedures. Morphological characteristics of the root cultivated by the direct sowing method were the same appearance as that by soil condition, but by the transplanting method main root branched off in all direction and the lateral root were more developed than by the direct sowing method. By pinching lignification in xylem on the main root were inhibited, but the dried weight of total root part and content (%DW) of saikosaponins in each part of the root were not shown to be significantly changed.