著者

中西 剛

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.127, no.3, pp.491-500, 2007 (Released:2007-03-01)

参考文献数

38

被引用文献数

2 8

---

Rodent models have great utility for evaluating the potential of environmental chemicals to alter human reproductive development. However, animal studies have some problems of species differences in extrapolating to human developmental toxicity induced by xenobiotics, because the placental endocrine functions in particular vary considerably among different species. For example, estrogen biosynthesis during pregnancy in humans is much different from that in rodents. In humans, ovarian function gradually declines after fertilization, as the placenta becomes the primary site of estrogen biosynthesis during pregnancy. In contrast to the process in humans, the ovary (not the placenta) is the main source of estrogen during pregnancy in rodents, because the placenta of rodents does not express the catalytic enzymes for estrogen biosynthesis, such as aromatase. The regulation of estrogen biosynthesis in the placenta is very important for human embryos because altering placental function can cause permanent effects on embryos. It has been suggested that rodents are therefore unsuitable for evaluating the potential effects of xenobiotics on the human reproductive system and developmental toxicity induced by the alteration of placental endocrine functions. Consequently, there is an urgent need to establish effective tools to evaluate the in vivo reproductive and developmental toxicity of environmental contaminants that disrupt the placental endocrine functions, including maintenance of local estrogen concentrations in the placenta. To resolve the problems, in this review we propose using transgenic mice, in which the transgene is controlled by placental-specific promoters, and local transgene systems into the placenta using viral vectors.

著者

岡田 壽太郎 森田 修之

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.100, no.5, pp.524-529, 1980-05-25 (Released:2008-05-30)

参考文献数

1

---

To deal with missing data in clinical tests, three methods (A, B, and E) were considered. Drug efficacy was estimated by (A) using only actual data, (B) using a previous value for a missing datum, and (E) using the value estimated by the equation (1) for a missing datum. [numerical formula] where S is the symptomatic severity (S0 is at the beginning), b is the recovery rate constant, θ is the number of days after the initiation of medical treatment, and subscript i means the i-th judgment. Based on theoretical calculations and analyses of nine sets of real data in ophthalmology, orthopedics and dermatology, (i) drug efficacy estimated by B was always smaller than by E, (ii) the difference in estimated drug efficacy between A and E was very small.

著者

山中 宏 江戸 清人 今野 昌悦

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.97, no.7, pp.p726-730, 1977-07

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Reaction of 2-cyano-4-methoxy-6-methyl- (I), 4-cyano-6-methoxy-2-methyl- (II), 5-cyano-4-methoxy-2-methyl- (III), and 5-cyano-4,6-dimethoxy-2-methylpyrimidine (IV) with Grignard reagents is described. While 2-cyano and 4-cyano derivatives (I, II) were transformed to the corresponding pyrimidinyl ketones as expected, 5-cyano derivatives (III, IV) were converted to the addition products, 5-cyano-6-ethyl-1,6-dihydro-4-methoxy-2-methyl- (VIIa) and 5-cyano-2-ethyl-1,2-dihydro-4,6-dimethoxy-2-methylpyrimidine (XI), respectively.

著者

川崎 和幸 山田 一磨呂 大江 孝範 鶴田 峯生 寺澤 道夫 今吉 朋憲 安永 幸弘 後藤 一洋

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.11, pp.827-834, 1989-11-25

被引用文献数

3

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The pro-drugs of α, 2-dimethyl-5H-[1] benzopyrano [2,3-b] pyridine-7-acetic acid (I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N, N-dimethylcarbamoyl-methyl α, 2-dimethyl-5H-[1] benzopyrano [2,3-b] pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.

著者

平原 敬三 安藤 直子 松石 哲郎 鈴木 信夫 寺尾 俊彦 倉田 宗司

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.108, no.9, pp.p860-866, 1988-09

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The addition of sodium oleate to antithrombin III (ATIII) produced complexes of ATIII and oleic acid by varying the acid concentration. During immunoelectrophoresis, ATIII shifted to the anode in the presence of sodium oleate. The reactivity of ATIII with anti human ATIII serum lowered as the sodium oleate level increased. However the reactivity with antibody obtained by immunization of rabbits with the mixture of sodium oleate and ATIII, was not lost on the immunoelectrophoresis. In acrylamide gel electrophoresis, ATIII separated into 6 bands with an increase in sodium oleate. The binding ratio of ATIII to heparin-Sepharose decresed in the presence of sodium oleate. In acrylamide gel isoelectrofocusing, the subtypes of ATIII having pI 5 showed high affinity to oleic acid. These high affinity subtypes also showed high affinity to heparin and thrombin. In fibrinogen agarose electrophoresis, ATIII lost its antithrombin activity depending on the increase of sodium oleate. By the determination of free fatty acids (FFA) in ATIII purified from normal plasma, we found that FFA would bind to ATIII in the normal plasma. Scatchard plot analysis indicated 7.6 binding sites of oleic acid per ATIII molecule. The results suggested that ATIII lost its activity by conformational change or interference in the thrombin binding site, and that the subtype of ATIII having pI 5 could be a significant carrier of plasma FFA.

著者

平澤 明 原 貴史 市村 敦彦 辻本 豪三

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.131, no.12, pp.1683-1689, 2011 (Released:2011-12-01)

参考文献数

44

被引用文献数

2 6

---

Free fatty acids (FFAs) are not only essential nutrient components, but they also function as signaling molecules in various physiological processes. In the progression of genomic analysis, many orphan G-protein coupled receptors (GPCRs) are found. Recently, GPCRs deorphanizing strategy successfully identified multiple receptors for FFAs. In these FFA receptors (FFARs), GPR40 (FFAR1) and GPR120 are activated by medium- to long- chain FFAs. GPR40 is expressed mainly in pancreatic β-cell and mediates insulin secretion, whereas GPR120 is expressed abundantly in the intestine and regulates the secretion of cholecystokinin (CCK) and glucagons-like peptide-1 (GLP-1), it promotes insulin secretion. Due to these biological activity, GPR40 and GPR120 are potential drug target for type 2 diabetes and selective ligands have been developed. In this review, we provide recent development in the field and discuss their physiological roles and their potential as drug targets.

著者

井上 隆夫 石館 八重子 藤田 正雄 久保 正良 福島 美雪 永井 正博

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.1, pp.41-46, 1978-01-25

被引用文献数

1

---

Chemical constituents of the leaves and stem bark of Acer nikoense MAXIM. (Aceraceae) were examined. β-Amyrin, β-sitosterol contaminated with campesterol and stigmasterol, and β-sitosterol glucoside were obtained from both parts of the plant. β-Amyrin acetate, quercetin, quercitrin, and ellagic acid were isolated from the leaves, and scopoletin, (+)-rhododendrol (VIII), (+)-catechin, and two new glycosides named aceroside I (XI), C_<25>H_<32>O_8,mp 170-171° (from acetone), [α] D-7.7°, and epi-rhododendrin (XII), C_<16>H_<24>O_7,mp 81-84°, [α] D -15.5°, from the stem bark. The absolute configuration of VIII was proposed to be S from empirical rule on optical rotation-chirality relationship. Hydrolysis of aceroside I (XI) afforded acerogenin A (XIII) as its aglycone, whose structure has already been reported. The structure of epi-rhododendrin (XII) was elucidated to be (S)-4-(p-hydroxyphenyl) butan-2-ol 2-β-D-glucopyranoside from chemical and spectral evidences.

著者

高橋 夏子 小林 正紀 板垣 史郎 平野 剛 武隈 洋 菅原 満 井関 健

出版者

日本薬学会

雑誌

Yakugaku Zasshi (ISSN:00316903)

巻号頁・発行日

vol.132, no.6, pp.777-783, 2012-06-01

---

The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner. However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs. We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs (cisplatin, carboplatin, paclitaxel and gemcitabine) was performed by the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The four anticancer drugs were grouped by IC50 values (inhibitory concentration, 50%) in a time-dependent manner and a concentration-dependent manner. The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs.

著者

柳澤 秀吉 高島 則一

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.481, pp.179-189, 1922-03-26

著者

大谷 道輝 川端 志津 假家 悟 内野 克喜 伊藤 敬 小瀧 一 籾山 邦男 森川 亜紀 瀬尾 巖 西田 紀子

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.122, no.5, pp.323-329, 2002-05-01

被引用文献数

1 13

---

The effect of the intake of 200g of grapefruit pulp (corresponding to one grapefruit) on the pharmacokinetics of the calcium antagonists nifedipine (NF) and nisoldipine (NS) were investigated in 8 healthy Japanese male volunteers. A crossover design was used for the study: group I did not ingest any grapefruit (control group); group II ingested grapefruit 1 h after drug administration; and group III ingested grapefruit 1 h before drug administration. The intake of grapefruit pulp increased the plasma concentrations of both NF and NS, an effect that has previously been reported with grapefruit juice. The increase was most marked when grapefruit was eaten before drug administration. For both NF and NS, subjects who ingested grapefruit 1 h before drug administration exhibited a greater C_<max> and AUC_<0-24> than did subjects in the control group. For NF, the C_<max> was 1.4 times higher and the AUC_<0-24> 1.3 times larger in group III than in group I. For NS, the C_<max> was 1.5 times higher and the AUC_<0-24> 1.3 times larger in group III than in group I. The increase in the AUC_<0-24> was significant for both drugs (p<0.05). The finding that the ratios of C_<max> and AUC_<0-24> for unchanged drug and metabolites did not vary greatly among the three groups for either drug suggests that the increase in serum concentration produced by grapefruit intake may be due to other factors than an inhibitory effect on drug metabolism. Also, the increases in C_<max> and AUC_<0-24> of NS produced by grapefruit intake were smaller than those produced by grapefruit juice intake, indicating that grapefruit pulp and juice have different effects on the pharmacokinetics.

著者

岡田 寿太郎 川島 嘉明

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.89, no.10, pp.1345-1351, 1969-10-25

---

Strychnine and brucine were extracted from slices of strychni seeds, cut into various sizes (#1-#4), in water at 27,37,and 47°. Results of analysis of extraction rate showed that the mechanism of extraction consists of washing, diffusion, and capillary extraction, but the capillary extraction occupies a small part. Mass transfer coefficients of these three mechanisms, which depend distinctly on temperature of the solvent, were determined.

著者

早川 順子 野田 直希 山田 貞二 宇野 圭一

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.104, no.1, pp.57-61, 1984-01-25

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Nux Vomica contains strychnine and brucine which showed a strong pharmacological activity. Therefore, an improved method of analyzing these compounds is of value. For determination of these compounds in Nux Vomica, titrimetry is employed on JPX. Then strychnine and brucine in Nux Vomica and commercial pharmaceutical preparations including Nux Vomica extracts were identified by thin layer chromatography (TLC) and determined using high performance liquid chromatography (HPLC). Samples were extracted with CHCl_3-MeOH (2 : 1). The extracts were passed through Sep Pak C_<18> cartridge and applied to TLC and HPLC. HPLCs of strychnine and brucine were carried out on Shodex ODS column and CH_3CN-H_2O (25 : 75) to which 1-heptanesulfonic acid was added as a counter ion for the solvent system. Recoveries from model preparations were more than 98%. This method was considered to be useful for the determination of strychnine and brucine in commercial preparations including Nux Vomica extracts.

著者

内山 充 鈴木 康男 福沢 健治

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.88, no.6, pp.678-683, 1968-06-25

被引用文献数

33

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Mechanism of antioxidation of tocopheronolactone, isolated as the quinonoid metabolic product of α-tocopherol, was examined. Tocopheronolactone was as effective as α-tocopherol in inhibiting the increase of TBA value during the in vitro incubation of α-tocopherol-deficient mouse liver homogenate, but the production of peroxide from unsaturated fatty acids irradiated with ultraviolet ray was not depressed by the sole addition of tocopheronolactone. Reduced tocopheronolactone depressed TBA value during the irradiation of unsaturated fatty acid with ultraviolet ray and reacted with the stable free radical α, α-diphenyl-β-picrylhydrazyl, but tocopheronolactone was not active. Reduced tocopheronolactone was oxidized to tocopheronolactone by free radical products of heme-catalyzed decomposition of cumene hydroperoxide. Tocopheronloactone in cytoplasm was reduced in 9000×g supernatant fraction but not in mitochondria, so that mitochondrial peroxidation was not inhibited by tocopheronolactone itself. Antioxidativeeffect of tocopheronolactone seems to appear after the biochemical reduction of the tocopheronolactone in vivo, followed by the reaction with free radicals and peroxides.

著者

安江 政一 加藤 義成 林 玉美 榊原 仁作

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.88, no.6, pp.738-741, 1968-06-25

被引用文献数

1

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Dried leaves of Acanthopanax sciadophylloides FRANCH. et SAV. were extracted with methanol and the water-soluble part of the extract was treated successively with solutions of lead acetate, basic lead acetate, and ammoniacal alkaline lead salt, as shown in Chart 1. myo-inositol, scyllitol, kaempferitrin, and antoside were isolated and identified. The constituents of these leaves were somewhat different according to the district where the materials came from. Utkin had suggested the structure of antoside as quercetin 3 (7)-glucosido-7 (3)-rhamnoside. Relative positions of glucose and rhamnose in the antoside molecule were now determined by enzymatic cleavage of rhamnose to give quercetin 3-glucoside (isoquercitrin) (Chart 2).

著者

北島 潤一 高森 靖 田中 靖子

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.3, pp.188-191, 1989-03-25

被引用文献数

1

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In fresh leaves of Acanthopanax sciadophylloides FR. et SAV. collected in June, the following substances were identified : (-)-β-caryophyllene, trans-β-farnesene, phytol, 1-dotriacontanol, taraxerol, a mixture of stigmasterol and β-sitosterol, trans-p-coumaric acid, trans-p-coumaric acid methylester, afzerin, kaemferitrin, kaempferol 7-O-α-L-rhamnopyranoside, 3-O-β-D-galactopyranosyl kaempferol 7-O-α-L-rhamnopyranoside and quercetin 3,7-O-bis-α-L-rhamnopyranoside. On the other hand, from the fresh leaves collected in August, trans-p-coumaric acid and kaempferol were obtained as aromatic compounds, but flavonoid glycosides were not detected. It is interesting that the constituents of these leaves were quite different between June and August.

著者

上釜 兼人

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.101, no.10, pp.857-873, 1981-10-25

被引用文献数

11

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Cyclodextrins are homologous series of cyclic oligosaccharides consisting of glucose units joined by α-1,4 linkages. One of the important characteristics of cyclodextrins is the formation of inclusion complexes with various guest molecules in solid phase and in solution, in which the guest molecules are included in the relatively hydrophobic cavity of cyclodextrins. The present review is mainly concerned with the possible utilities of cyclodextrins in pharmaceutical fields. A number of examples such as improvements of solubility, chemical stability, bioavailability, etc. are presented. These informations will provide a rational basis for design of formulation and a means for improving efficacy of drug activity.

著者

鹿野 美弘 縦 青 小松 健一

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.111, no.1, pp.32-35, 1991-01-25

被引用文献数

1

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A crude drug, Evodia fruit (goshuyu) was processed to detoxicate and reduce the bitter taste. Following the procedure described in Shokanron (傷寒論), Evodia fruit was washed in hot water, and then dried. The alkaloid contents of processed Evodia fruit was analyzed by high performance liquid chromatography. The result shows that the content of hydroxyevodiamine decreased to 0.55 times, while the content of rutaecarpine and evodiamine hardly change in the final processed material. However, evocarpine content increased to 1.3 times comparing with the untreated Evodia fruit. The phenomena was ascribed to the flowing-out of the water-soluble portion, and also the weight of extract and the intense of bitterness in the processed fruit were reduced to about 1/3 times.

著者

小菅 卓夫 横田 正実 長沢 道男

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.98, no.10, pp.p1370-1375, 1978-10

被引用文献数

3

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Aconite root (Bushi in Japanese) from Aconitum japonicum THUMB. has long been used as one of the most important herbs as a heart stimulant, diuretic agent ; and anodyne in Chinese medichine. Isolation and identification of the cardiac principle predicted by Yakazu are described. In the isolation process, the Yagi-Hartung method using frog heart was found to be useful for pharmacological measurement of cardiac activity of the material. The material was water soluble and was fairly unstable, especilly in a basic medium, and was tightly adsorbed on charcoal, alumina, silica gel, and cellulose powder, indicating that these agents are not useful for the separation. Isolation of the material was finally achieved by the limited combination of gel filtration through Sephadex LH-20 and counter current distribution, and colorless plates, mp 260°, were obtained as HCl salt. This principle stimulates frog heart even 1 : 10^<-9> dilution, and it was designated as Higenamine. Higenamine was identified as dl-demethylcoclaurine (II) from the spectral data and by comparison with synthesized authentic sample.

著者

和田 浩二

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.122, no.11, pp.929-956, 2002-11-01

被引用文献数

13

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The chemical constituents of <i>Aconitum yesoense</i> var. <i>macroyesoense</i> and <i>Aconitum japonicum</i> were examined using high-resolution spectral analysis. Twelve novel alkaloids were isolated from <i>A. yesoense</i> var. <i>macroyesoense</i> together with 20 known alkaloids. Eight novel alkaloids were isolated from <i>A. japonicum</i> together with 15 known alkaloids. An HPLC-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method was useful for the simultaneous determination of 21 <i>Aconitum</i> alkaloids found in <i>A. yesoense</i> var. <i>macroyesoense</i> and A. <i>japonicum</i>. These compounds were fairly stable under the conditions used, and the protonated molecules or fragment ions characteristic of the molecule appeared as base peaks in the mass spectra and were used for selected ion monitoring. HPLC-APCI-MS is a very promising approach for structural investigations of positional isomers and stereoisomers. This method was applied successfully to stereoisomeric <i>Aconitum</i> alkaloids differing in configuration at C-1, -6, or -12. Comparison of the APCI spectra showed that the abundance of fragment ions was significantly higher for the C-1, -6, or -12 β-form alkaloid than for C-1, -6, or -12 α-form alkaloid. The main alkaloid constituents in the root of <i>A. yesoense</i> var. <i>macroyesoense</i>, <i>Aconitum</i> alkaloids of the C₂₀-diterpenoid type, kobusine and pseudokobusine, and their acyl derivatives were examined for their peripheral vasoactivities by measuring laser-flowmetrically the cutaneous blood flow in the hind foot of mice after intravenous administration. It is thought that the hydroxyl groups of alkaloids, especially a free OH group of pseudokobusine at C-6, were important for action on the peripheral vasculature leading to dilatation, and the results indicated that esterification of the hydroxyl group at C-15 with either anisoate, veratroate, or <i>p</i>-nitrobenzoate may contribute to enhancement of the activity of the parent alkaloids.<br>

著者

坂井 進一郎 高山 広光 岡本 敏彦

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.6, pp.647-656, 1979-06-25

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Reinvestigation of the alkaloidal constituents of Aconitum japonicum THUNB. of Mt. Takao (Tokyo) was made. In addition to the reported constituents, i.e. isohypognavine, delcosine and dehydrodelcosine, two known compounds, isotalatizidine and condelphine, were isolated. Furthermore, five new bases, i.e. 11-acetylisohypognavine, diacetylisohypognavine, 14-acetyltalatizamine, takaosamine and takaonine, were isolated and their structures were elucidated. Takaosamine was proved to be 18-O-demethyldelcosine from the spectroscopic study on the parent material and the acetyl derivatives, and from the chemical correlation with known diterpene alkaloids, gigactonine and delsoline. The structure of takaonine was deduced to be 2,3-dehydro-14-dehydrodelcosine on the basis of ^<13>C-nuclear magnetic resonance spectral evidence and the derivation to the known diterpene alkaloid, delcosine, by catalytic hydrogenation.