著者

山野 光久

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.45, no.4, pp.327-332, 2009-04-01 (Released:2018-08-26)

参考文献数

18

著者

山崎 康夫

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.40, no.2, pp.121-125, 2004-02-01 (Released:2018-08-26)

参考文献数

23

著者

小森 浩二 塙 由美子 山本 淑子 古前 竜平 山崎 裕己 中野 祥子 三田村 しのぶ 宮﨑 珠美 菊田 真穂 高田 雅弘 首藤 誠

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.133, no.8, pp.905-911, 2013

被引用文献数

2

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&nbsp;&nbsp;Loxoprofen (Loxonin^&reg;), an antipyretic painkiller, was approved as an over-the-counter (OTC) drug (Loxonin^&reg;-S) in January 2011. With regard to self-medication using OTC drugs, the information that pharmacists provide to consumers is very important. Although loxoprofen is a very versatile drug and can be used during breastfeeding, information regarding its mammary gland transfer is inadequate. In this study, we established a simple method to evaluate mammary transfer of drugs, and compared loxoprofen's mammary gland transfer with that of aspirin. Loxoprofen 12 mg/kg and aspirin 132 mg/kg was orally administered to mother mice (ddY), and blood and milk samples were collected. Twenty microliters of ethanol was added to the blood and milk samples (10 &mu;L), and the mixture was centrifuged for 15 min (12000 <i>g</i>); the supernatant was analyzed by high-performance liquid chromatography. Since aspirin was immediately metabolized, we analyzed salicylic acid concentrations. Maximum concentration of loxoprofen was observed at around 15 min after its oral administration, with the concentrations in the blood and milk being 2.9 and 0.5 &mu;g/mL, respectively. The drug was metabolized promptly thereafter. In contrast, maximum concentration of salicylic acid was observed at 30 min after aspirin administration, with the concentrations in the blood and milk being 187.2 and 64.4 &mu;g/mL, respectively. These concentrations remained constant from 60 to 120 min. Salicylic acid could be detected 240 min after aspirin administration. Thus, mammary gland transfer of loxoprofen is lower than that of aspirin, suggesting that loxoprofen does not accumulate in milk.<br>

著者

山口 卓朗

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.54, no.11, pp.1081, 2018 (Released:2018-11-01)

参考文献数

3

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X線結晶構造解析法は,最も有力な分子構造解析法の1つであるが,解析対象化合物の結晶化が必須であるという大きな制約がある.この制約を解消する画期的な材料として登場したのが,結晶スポンジ(crystalline sponge: CS)である.CSは多孔性錯体結晶であり,孔の内部に他の化合物を取り込むことができる.解析対象化合物の溶液にCSを浸すと,溶液から取り込まれた化合物が孔の内部で単結晶のように規則正しく整列する仕組みになっており,そのままX線結晶構造解析に用いることができる.CSを用いた構造解析法は結晶化が困難な化合物や液状化合物にも適用できることから,天然物化学や合成化学の研究を迅速化すると考えられている.しかしながら,CS法にも1つ問題がある.それは,CSに取り込まれにくい化合物,いわゆる親和性が低い化合物には,取り込みを促す条件検討が必要となるため,親和性が高い化合物と比較して測定までに長時間を要することである.そこでWadaらは,効率的にCS法を用いるために,多数の化合物の中から親和性の高い化合物を選別する新規ワークフローを開発したので紹介する.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Inokuma Y. et al., Nature, 495, 461-466(2013).2) Wada N. et al., Angew. Chem. Int. Ed., 57, 3671-3675(2018).3) Kersten R. D. et al., J. Am. Chem. Soc., 139, 16838-16844(2017).

著者

壬生 百香

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.53, no.11, pp.1104-1105, 2017 (Released:2017-11-01)

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私は、平成15年3月に岐阜薬科大学薬学部を卒業したあと、奈良先端科学技術大学院大学バイオサイエンス研究科修士課程、三重県庁勤務、早稲田大学ロースクール等を経て、平成25年に弁護士としてのキャリアを開始した。これまでの取扱分野は、医薬分野、知的財産権、企業法務から一般民事、家事事件まで多岐にわたる。本稿では、いくつかの弁護士の業務について話すことで、弁護士の仕事を読者の皆さんに紹介したい。

著者

KITAZATO KENJI TAKEDA SETSUO UNEMI NORIO

出版者

公益社団法人 日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:0386846X)

巻号頁・発行日

vol.5, no.10, pp.803-810, 1982

被引用文献数

9

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1, 3, 3, 5, 5-Pentaziridino-1-thia-2, 4, 6-traiza-3, 5-diphosphorine-1-oxide (SOAz), a new antitumor agent, was evaluated for antitumor activity against various mouse- and rattumor systems. The optimal treatment regimens of SOAz (i.p.) gave 262% and 134% increase in life span (ILS) in mice P338 leukemia and L1210 leukemia implanted intraperitoneally, respectively, and 239% ILS in rats with Yoshida sarcoma of which 86% survived for 60 d after intraperitoneal tumor implantation. The compound showed a definite activity against Lewis lung carcinoma implanted intravenously. The compound also exhibited 80-100% inhibition of tumor local growth in all of four experimental tumor systems used in the present study. In contrast to cyclophosphamide, SOAz was active against B16 melanoma and Meth A, and demonstrated high activity against a subline of L1210 leukemia resistant to cyclophosphamide.

著者

桑田 一夫

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.132, no.8, pp.873-879, 2012 (Released:2012-08-01)

参考文献数

17

被引用文献数

1

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We developed a theoretical framework for the regulation of biological macromolecules using the logically designed compounds. According to the cohomology theory, algebraic objects can be translated into geometrical ones. Successfully established quantum theory at 20th century, which essentially deals with the non-commutative nature of the space, also suggests the non-commutative topology of biological space. Arithmetic geometrical representation of the molecules as well as the macroscopic membranous structures would uncover their structural groups in Hilbert space. In order to construct the concrete image of biological space, here we combined quantum chemical (QC) model, all-atom (AA) model and coarse grained (CG) model, into one program designated ‘NAGARA’. These three models can be arranged in an arbitrary manner to yield the desired statistical ensemble. For example, QC model was applied to the optimization of the chemical structure of anti-prion lead compound GN8. Arithmetic geometrical representation of these algebraic models is in progress.

著者

濵田 芳男

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.133, no.10, pp.1113-1120, 2013-10-01 (Released:2013-10-01)

参考文献数

23

被引用文献数

1 1

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This review discusses the importance of quantum chemical interactions in biomolecules for medicinal science and their relevance to the author's β-secretase (BACE1) inhibitor drug discovery research. Although molecular mechanics/dynamics (MM/MD) methods are available in many in silico design tools used for drug discovery, they cannot accurately evaluate quantum effects between biomolecules and drugs. The key roles of biomolecular quantum chemical interactions in drug discovery are discussed using the arginine side chain as an example. Arginine is recognized as a charged amino acid in commonly used drug design software, unlike other amino acids with π-electron orbitals, such as phenylalanine, tyrosine, and tryptophan. Quantum chemical interactions via the arginine side chain are crucial for molecular recognition, and are found in many X-ray crystal structures, such as protein-protein, protein homodimer, RNA aptamer-protein, and enzyme-inhibitor complexes. This review describes the essential role of quantum chemical interactions via the arginine side chain in the mechanism of BACE1 inhibition, and proposes an “electron donor/acceptor bioisostere” concept for medicinal science based on quantum chemical interactions. Several potent BACE1 inhibitors, as well as the first peptides with BACE1 inhibiting activity were designed and synthesized based on studies of quantum chemical interactions via arginine side chain and the “electron donor bioisostere” concept.

著者

中村 和則 城村 綾子 織田 実 猪 好孝 内山 浩之 大谷 尚也 宮崎 裕行 来海 正輝 秋澤 有四郎 岡 俊範

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.3, pp.201-212, 1995-03-25 (Released:2008-05-30)

参考文献数

28

被引用文献数

3 7

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Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 μM for trypsin, 0.029 μM for pancreatic kallikrein, 0.61 μM for plasma kallikrein, 0.57 μM for plasmin, 2.5 μM for thrombin, 20.4 μM for factor Xa and 6.4 μM for Clr. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for Cls, and Ki values for these proteases were 0.021 and 0.18 μM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 μM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 μM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 μM, while camostat revealed no inhibition by concentrations up to 1 μM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 μM, respectively, the corresponding values for camostat being 350 and 150 μM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and Cls in complement pathway.

著者

佐々木 信行 緑川 淳 荒川 勝雅

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.8, pp.544-550, 1992-08-25 (Released:2008-05-30)

参考文献数

8

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FUT-187 (I), 6-amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, is a new synthesized proteinase inhibitor. Decomposition kinetics and photoreactivity of I in aqueous solution were studied. In aqueous solution, I was hydrolyzed to its moieties, [4-(4, 5-dihydro-1H-imidazol-2-yl)amino] benzoic acid (IABA) and 6-amidino-2-naphthol (AN). The hydrolysis followed a pseudo-first order reaction. I was stable under acidic condition between pH 2 and pH 3 and decomposed by irradiation from xenon light to form IABA, AN and compound II. The structure of II was studied by nuclear magnetic resonance, infrared, mass and ultraviolet spectra and identification tests. It was shown that II was 6-amidino-2-hydroxy-1-naphthyl[4-(4, 5-dihydro-1H-imidazol-2-yl)amino]-phenyl ketone, benzophenone derivative, produced by photorearrangement reaction of I.

著者

多比良 和基 安田 行寛 新藤 恭司 三谷 鳴夫 赤沢 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.100, no.3, pp.272-279, 1980-03-25 (Released:2008-05-30)

参考文献数

19

被引用文献数

2 2

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The biological fate of 4-butyl-4-(β-carboxypropionyloxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione : suxibuzone (SB) was studied in rats and beagle dogs. Furthermore, the effects of SB on liver microsomal drug metabolizing enzyme systems in rats were compared with those of phenylbutazone (PB), after daily oral administration of SB or PB for 1 week. 1) The biological fate of SB was different in rats and dogs and in the former a sex difference was noted. 2) Liver microsomal drug metabolizing enzyme systems were induced especially in male. 3) No difference between the two drugs was noted. However, when a single oral dose of SB was administered, keeping the PB schedule the same as above, the plasma half-life of PB was markedly shortened and maximum plasma levels of metabolites were rapidly reached. These results suggest that the biological fate of SB was stimulated by the enhancement or induction of liver microsomal drug metabolizing enzyme systems due to PB and its metabolites after daily oral administration.

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

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.12, pp.1186-1200, 1979-12-25 (Released:2008-05-30)

参考文献数

20

被引用文献数

4 5

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The biological fate of 4-butyl-4-(β-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 γ-hydroxyphenylbutazone (γ-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, γ-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 γ-Hydroxy-PB and in urinary excreted percent of γ-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 γ-Hydroxy-PB had no effect on its action.

著者

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

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.111, no.9, pp.499-503, 1991-09-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

3 6

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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.

著者

堀 久男

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.50, no.1, pp.54-58, 2014 (Released:2016-02-01)

参考文献数

25

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有機フッ素化合物は耐熱性,耐薬品性,界面活性等の優れた性質を持つ.このため様々なところで使われているが,近年になって環境残留性や生体蓄積性,さらには廃棄物の分解処理が困難といった負の側面が顕在化しつつある.環境中で検出されているのは主に界面活性剤として用いられてきたペルフルオロアルキルスルホン酸類(PFAS類,CnF2n+1SO3H)やペルフルオロカルボン酸類(PFCA類,CnF2n+1COOH),およびそれらの誘導体である.中でもペルフルオロオクタンスルホン酸(C8F17SO3H,PFOS)やペルフルオロオクタン酸(C7F15COOH,PFOA)といった化合物は生体蓄積性が高いため,使用や排出に関する規制(自主規制も含む)が世界的に進行している.このような有機フッ素化合物の環境リスクの低減のためには,有害性の度合いに応じて排水や廃棄物の無害化を行う必要があるが,炭素・フッ素結合は炭素が形成する共有結合では最強なため容易に分解しない.焼却は可能であるものの,高温が必要であるだけでなく,生成するフッ化水素ガスが焼却炉材を損傷する問題がある.これらの物質をフッ化物イオン(F-)まで分解できれば,既存の処理技術により環境無害なフッ化カルシウムに変換できる.フッ化カルシウムの鉱物は蛍石で,硫酸処理によりフッ素ポリマーを含むすべての有機フッ素化合物の原料であるフッ化水素酸になるため,フッ素資源の循環利用にも寄与できる(図1).これまでにも電子線照射やプラズマ等の高エネルギー的な手法を使えば,フッ素ポリマーでさえ分解できることは知られていた.しかしその場合,毒性が非常に高いペルフルオロイソブチレン(CF3C(CF3)CF2,PFIB)や温暖化係数が二酸化炭素の数千倍のテトラフルオロメタン(CF4)等の有害ガスの発生が懸念されている.以上の背景から,我々はPFCA類やPFAS類,さらにはそれらの誘導体について種々の比較的穏和な反応手法を開発し,F-までの完全分解,すなわち無機化を達成してきた.本稿ではそれらについて,他の研究者の報告例も交えて報告したい.

著者

馬場 貴志

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.50, no.9, pp.915, 2014 (Released:2016-09-17)

参考文献数

4

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宇宙航空研究開発機構(JAXA)をはじめ,アメリカ航空宇宙局(NASA),欧州宇宙機関(ESA)などの各国宇宙機関は,火星探査や月面居住の実現へ向けたロードマップを作成し,さまざまな面からの研究・開発を進めている.ヒトが宇宙で健全に生活するためには,安全性をはじめとする様々な面からの検討が必要であり,微生物についても大きなトピックの1つとなっており,国際宇宙ステーション「きぼう」日本実験棟においても微生物モニタリングが実施されている.宇宙などの微小重力下においては,細菌の病原性が上昇するといった報告もあり,もし宇宙において病原微生物が増殖した場合,重大な事態を引き起こす可能性があることから,微生物への影響に関する研究が行われている.一方で,宇宙飛行によってヒトの免疫機能が低下することも報告されており,これは日和見感染のリスクが上昇する可能性があることを示している.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Ichijo T. et al., Microbes Environ., 28, 264-268 (2013).2) Wilson J. W. et al., PNAS., 104, 16299-16304 (2007).3) Borchers A. T. et al., Nutrition, 18, 889-898 (2002).4) Crabbe A. et al., Plos one, 8, e80677 (2013).

著者

小野 秀樹 岡村 真彩 福島 章紘

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.138, no.9, pp.1201-1215, 2018-09-01 (Released:2018-09-01)

参考文献数

82

被引用文献数

9

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The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as “clinically significant adverse reactions”, and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

著者

秋田 英万

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.11, pp.1059_1, 2016

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グリベラ(Glybera^&reg;:ユニキュア)は,2012年にEuropean Medicines Agency(EMA)より認可された,先進国初の遺伝子治療薬である.アデノ随伴ウイルス(adeno associate virus:AAV)を用いた遺伝子導入技術を基盤としている.本薬は,リポ蛋白質リパーゼ欠損症(lipoprotein lipase deficiency:LPLD)を抱え,再発性急性膵炎を発症する患者を対象としている.極めて希少な遺伝性疾患が対象となっているものであり,多くの患者が恩恵をうけるものではないが,永年停滞してきた遺伝子治療の重要性を再認識させる歴史的な快挙である.

著者

金沢 貴憲

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.138, no.4, pp.443-450, 2018-04-01 (Released:2018-04-01)

参考文献数

13

被引用文献数

6

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In general, the blood-brain barrier (BBB) poses a major challenge to drug development efforts targeting brain/central nervous system (CNS) diseases, since it limits the distribution of systemically administered therapeutics to the brain/ CNS. Therefore, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both the clinical and pharmaceutical fields. Intranasal administration has been noted as a method for noninvasive delivery of a drug to the brain/CNS by bypassing the BBB via the “nose-to-brain” route. This nose-to-brain delivery system has the potential to be highly versatile, and a combination of this system with new drugs and siRNA shows promise in the treatment of CNS diseases. Cell-penetrating Tat peptide-modified block copolymer micelles have the potential for improving mucosal permeability and nose-to-brain transport efficiency. In addition, nano-sized drug carriers can improve nose-to-brain delivery through their ability to increase the stability of encapsulated drugs against biological degradation in the nasal cavity and brain/CNS. In this review, we introduce the assessment of and mechanisms for delivery to the brain after intranasal drug/siRNA administration with our cell-penetrating peptide-modified nano-sized polymer micelles. Our findings show that the use of polymer micelles with surface modification by cell-penetrating peptides for intranasal administration enables the noninvasive delivery of therapeutic agents to the brain/CNS by increasing the nose-to-brain transfer of the drug or siRNA administered from the nasal cavity.

著者

清水 貴壽

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.47, no.4, pp.345-346, 2011-04-01 (Released:2017-05-26)

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.7, 1998