著者

小林 和弘 織田 範一 伊藤 磯雄

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.101, no.9, pp.806-813, 1981-09-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

1 1

---

As the initial study of variations of skeletons of antitumor antibiotics, simple synthesis of naphtho [2, 3-g] quinolines (IIIa, b, VIII) and naphtho [2, 3-g] quinoxalines (XIIIa, b), which are novel heterocyclic ring systems, was carried out by Diels-Alder reaction of 1, 2-dimethylenecyclohexane with quinoline-5, 8-diones (Ia-c) or quinoxaline-5, 8-diones (IIa, b). Air oxidation of these Diels-Alder adducts gave tetrahydro naphtho [2, 3-g] quinolines (IVa, b, IX) and tetrahydronaphtho [2, 3-g] quinoxalines (XVa, b). The Diels-Alder adducts and aromatized compounds were converted into the corresponding diacetoxynaphtho [2, 3-g] quinolines (VI, VII, X) and diacetoxynaphtho [2, 3-g] quinoxalines (XVII, XVIII).

著者

小林 和弘 織田 範一 榊原 仁作

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.103, no.2, pp.165-172, 1983-02-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

1 1

---

Ethyl 5-hydroxybenzo [α] phenazine-6-carboxylates (IIa, b) were prepared by the condensation of ethyl 1, 4-dihydro-1, 4-dioxo-3-methoxy-2-naphthoate (I) with o-phenylene-diamines. Acylations and alkylations of IIa, b gave the corresponding o-acyl and alkyl compounds (IIIa-k). The reaction of IIa, b with ethanolamine gave β-hydroxyethyl-carboxamides (Va, b). Compound Va was converted into β-chlorinated compound (VIa), whose chlorine was substituted by dialkylamines to give ethylenediamine-type amides (VIIa, b, c). Compounds VIId and VIIe were obtained by the reaction of IIb with dialkylalkylenediamines. Oxidation of IIa, b afforded N-oxides (IXa, b). The antimicrobial activities of all synthetic compounds were tested by paper discagar diffusion assay. Compounds IIId, e, g, VIIa and IXa showed inhibitory activities to T. interdigitale and IXa to C. albicans.

著者

小林 和弘 織田 範一 榊原 仁作

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.103, no.4, pp.473-479, 1983-04-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

1 1

---

Ethyl 1, 4-dihydro-1, 4-dioxo-3-methoxy-2-naphthoate (I) is condensed with amidines, 2-aminopyridines and 3-aminopyrazole, to give new tetracyclic quinones (IIIa-c and VI) containing nitrogen atom and hydrogenation of IIIa and IIIb over Pd-C or Raney-Ni afforded 1, 2, 3, 4-tetrahydro (IXa, b) or 1, 2, 3, 4, 7, 8, 9, 10-octahydrobenzo[g]pyrido[2, 1-b]quinazoline (Xa), respectively. Benzo[g]pyrido[2, 1-b]quinazoline derivatives except for Xa showed inhibitory activities to S. aureus and T. interdigitale.

著者

小松 俊哉 矢野 雅士 稲田 治明 岩本 光男 岡田 一男 鈴木 健一

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.12, pp.1016-1021, 1995-12-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

3 3

---

The two mono-hydroxylated metabolites of 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of two tricyclic ketones, 9-amino-1, 2, 3, 5, 6, 7-hexahydro-8H-cyclopenta [b] quinolin-8-one and 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b]-quinolin-1-one, with NaBH4 afforded the corresponding racemic alcohols. The optically active mono-hydroxylated metabolites, (+)-9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinolin-8-ol and (+)-9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinolin-1-ol, were obtained by optical resolution of each racemic alcohol using (+)-di-p-toluoyl-D-tartaric acid.

著者

本間 克明 酒井 律子 武島 晶子 島森 美光 早瀬 幸俊

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.124, no.10, pp.693-697, 2004-10-01

参考文献数

5

被引用文献数

1

---

生活環境の改善や医学の進歩等により, わが国の平均寿命は平成13年では男性78.07年, 女性84.93年となり, 1)世界有数の長寿国となっている. そして, 65歳以上の高齢者人口は平成12年でおよそ2200万人と総人口の17.4%を占めており, 平成27年には26%台となり, さらに平成42年には29.6%, 平成62年には35.7%に達すると推計されている. 2)このような急速な高齢化の進展や疾病構造の変化等によりわが国の医療をとりまく環境は大きく変化しており, それに伴い国民医療費は年々増大し, 平成11年度には約30兆円に到達した. 年齢階級別国民医療費を平成12年度で見ると, 65歳以上の医療費が約12兆円で, 実に50%を占めるに至っており, これを1人当たりの医療費で見ると, 15歳から44歳が約7万円, 45歳から64歳が約19万円であるのに対して, 65歳以上では約54万円, 70歳以上では約63万円, 75歳以上では約70万円と15歳から44歳及び45歳から64歳の医療費に比べて, それぞれ約3倍から10倍高くなっている. 3)この原因としては高齢者は受診率が高く, また重症化し易く, かつ治療には長期間かかることなどが考えられている.

著者

斎藤 裕久 浜名 政和

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.1, pp.23-29, 1979-01-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

1 3

---

Nitration of 1-cyanoisoquinoline 2-oxide (1) with potassium nitrate and sulfuric acid gave 5-and 6-nitro derivatives (2 and 3). The reaction was affected by the concentration of sulfuric acid, and 3 was obtained in small yields as the sole product from the reactions in the 85% acid at 70°. Nitration with fuming nitric acid (d=1.50) led to the formation of 3 in fairly good yields together with small amounts of 8-nitro derivative (7). Further, nitration of isoquinoline 2-oxide (9) with fuming nitric acid was found to give 5-, 6- and 8-nitro derivatives (10, 11 and 12). The orienting effect of the N-oxide function is apparently operative in the formation of 11 and 12.

著者

高 夢璇 佐藤 元重 池谷 裕二

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.6, pp.809-813, 2018-06-01 (Released:2018-06-01)

参考文献数

7

被引用文献数

2

---

During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as “seizure-inducing” drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

著者

渡部 恵 杉浦 宗敏 清野 敏一 光永 義治 中村 均 山田 安彦 土屋 文人 大江 和彦 伊賀 立二

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.10, pp.841-847, 2002-10-01

参考文献数

4

被引用文献数

4 4

---

In the computerized prescription order entry system, it has been pointed out that a physician's input mischoice for medicine is one of the causes of medication errors. We therefore investigated the input mischoices by physicians at the time of writing prescriptions. Subsequently, the number of input characters in a prescription order was changed to three characters from two characters. Furthermore, 105 items of high-alert medications, which are likely to result in injury if errors occur, were established. A warning screen display system that requests reconfirmation of the effect, name, usage, and dosage of those medicines was also built. It was found that 70% of input mistakes were caused by choosing the medicine displayed immediately above or below the desired drug. By changing the number of input characters of a prescription order to three characters from two characters, the rate of specification of a trademark improved sharply from 36% to 85%. Consequently, the rate of choice of a drug with another trademark decreased significantly from 0.028% to 0.0047%. In 5% of cases when the warning screen was displayed for a high-alert medicine, the prescription was stopped, and 25% were changed to other medicines. The above results show that the system that requires the input of three or more characters for the physician order entry and displays a warning screen for high-alert medicines is useful in preventing mischoices at the time of prescription input.<br>

著者

狭間 研至

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.1, pp.17-20, 2012-01-01 (Released:2012-01-01)

参考文献数

3

被引用文献数

3 2 1

---

In Japan, the proportion of elderly people had reached up to 23% in 2009. The number of elderly people in long-term nursing homes or nursing facilities will increase in the next decade. By 2025, the majority of the elderly people would have developed cancer, stroke, cardio-vascular diseases, and dementia. Almost all of them would be treated with prescribed drugs. They would also have dysphagia and have difficulties in remembering their medications in the long term. Therefore, for the benefit of such a community, the work force, especially in the field of drug distribution, will need to be increased to prevent the incidence of patients who forget to take their medications. Further, the educational curriculum for pharmaceutical students has been changed to a new version, and some Japanese pharmacy shops have been switching over to “Pharmacy 3.0,” which is the next generation model. In this pharmacy, the pharmacists will play an additional new role; they will not only dispense drugs but also support home recuperation leveraging some vital signs and physical assessments. In my opinion, this novel scheme of medical service developed with pharmacists playing this new role may be a boon to the patient/elderly community in Japan who are facing the collapse of healthcare systems. In conclusion, Collaborative Drug Therapy Management (CDTM) in the practice of the pharmacists is essential for increasing the efficiency of the Japanese healthcare systems.

著者

藤田 路一 川瀬 清

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.71, no.11, pp.1229-1231, 1951-11-25 (Released:2010-02-19)

参考文献数

5

---

For one year between 1950 and 1951, specific weight of tissue powder of rhizomes without roots of Scopolia japonica Maxim., growing wild in a certain area, was measured by Koketsu's powder method and a marked seasonal variation was found to exist (Table I and Fig. 1). The cause of this variation was found to be due to the amount of starch accumulated (Table I and Fig. 2). Consequently, it was proposed that tne customary representation of its component content by the weight percentage was of little physiological significance. Therefore, the determined values of total alkaloid and total nitrogen were shown by the volume percentage calculated from specific weight of tissue powder (Table I and Fig. 3). From these values, a large seasonal variation of alkaloidal content could not be detected.

著者

柊元 巌

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.139, no.1, pp.75-79, 2019-01-01 (Released:2019-01-01)

参考文献数

13

---

Persistent infection with oncogenic human papillomaviruses (HPVs) is necessary for the development of cervical cancer, although the accumulation of somatic mutations in the host genome is also required for the generation of invasive cervical cancer. Recent studies have demonstrated concomitant genetic changes in the HPV genome; however, their relevance to cervical carcinogenesis is poorly understood. Here we review our recent study investigating the within-host genetic diversity of HPV and its relationship with cervical cancer progression through deep sequencing analyses of viral whole-genome sequences in clinical specimens. Intriguingly, HPV genomes within individual clinical samples show an astonishingly high level of nucleotide variation across all histological grades of cervical lesions. Among the various substitution patterns, C-to-T and C-to-A substitutions are the predominant changes observed in the HPV genomes. Analysis of the trinucleotide context for substituted bases reveals that TpCpN (N is any nucleotide), which is a preferred target sequence for the cellular apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) proteins, is the major target for C-to-T substitutions in the HPV genomes. These mutational signature analyses strongly imply that within-host HPV variations are mostly generated through APOBEC-mediated mutagenesis. Because the HPV oncogenes E6 and E7 harbor APOBEC-related mutations, we propose a potential role for APOBEC-mediated mutagenesis in cervical carcinogenesis.

著者

中西 秀之 樋口 ゆり子 川上 茂 山下 富義 橋田 充

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.129, no.12, pp.1433-1443, 2009-12-01 (Released:2009-12-01)

参考文献数

58

被引用文献数

3 3

---

Transposons are mobile genetic elements that move between or within vectors and chromosomes. For the transposition, an enzyme called transposase recognizes transposon-specific terminal inverted repeat sequences (IRs) located on both ends of transposons, and remove them from their original sites and, integrates them into other sites. Because of this feature, transposons containing genes of interest between their two IRs are able to carry the genes from vectors to chromosomes. Transposons are promising systems for chromosomal integration because they can not only integrate exogenous genes efficiently, but also be transfected to a variety of cells or organs using a range of transfection methods. In this review, we focused on the therapeutic application of transposons. A few transposons can integrate transgenes into mammalian chromosomes. They have been used in preclinical studies of gene therapy and cell therapy. In addition, they have recently been used for generation of induced pluripotent stem cells. Transposon-based integrative vector systems have two components. One is the transposon containing transgenes, and the other is the expression cassette of the transposase. Both viral and non-viral vectors have been used to deliver these two components to mammalian cells or organs, and sustained transgene expression has been achieved. Transposon-mediated sustained transgene expression has also produced therapeutic effect in disease models of hereditary and chronic diseases. Although transposon-based integrative vector systems have problems, such as insertional mutagenesis, studies to overcome these problems have been progressing, and these vector systems will become indispensable tools to cure refractory diseases.

著者

砂田 久一

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.8, pp.1087-1107, 2008-08-01 (Released:2008-08-01)

参考文献数

49

被引用文献数

3 4

---

My main research fields are powder technology, especially solid dosage form, from basic ones to applied ones. Basic ones are physical properties of powder and its packing, compression and computer simulation. Applied ones are preparation and evaluation of granulation, tableting, improvement of solubility of water poor-soluble drug, controlled release tablet and fast disintegrating tablet in the oral cavity. As the chair man of the Standard Formulation Research Council, I have obtained many variable and excellent results. Several results are shown as follow.

著者

森田 直賢 清水 岑夫 竹崎 孝行

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.10, pp.1277-1280, 1968-10-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

9 12

---

A new glycoside (I), C24H26O18·11/2H2O, mp 274-275°, was isolated from Chrysosplenium grayanum MAXIM. (Japanese name"Nekonomeso"), and a glycoside (II), C24H26O12·2H2O, mp 175-176°, from C. flagelliferum FR. SCHM. (Japanese name"Tsurunekonomeso"). I was determined as oxyayanin-A (5, 2', 5'-trihydroxy-3, 7, 4'-trimethoxyflavone)-2'-glucoside, and was named chrysosplenoside-A, and II as pendulin (5, 4'-dihydroxy-3, 6, 7-trimethoxyflavone-4'-glucoside).

著者

朝比奈 泰彦 淺野 順太郎

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.50, no.11, pp.1103-1108, 1930

著者

柴田 丸 吉田 玲子 本橋 幸子 福島 正子

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.93, no.12, pp.1660-1667, 1973-12

被引用文献数

8

---

Crude saikosides did not affect the LD_<50> value of sodium hexobarbital in mice. It also exerted a protective effect on the pylorus-ligated ulcer of the rat with inhibiting gastric secretion. The cure of chronic ulcer produced by the injection of dilute acetic acid into the rat gastric wall was promoted by crude saikosides. Saikogenin A showed a potent effect of decreasing spontaneous motor activities of the mice treated with methamohetamine hydrochloride. It had a significant antitussive, hypothermic, and antipyretic effect, and inhibition of acetic acid-induced writhing responses. In addition, salikogenin A strongly reduced a carrageenin-induced rat paw edema, without any local irritaition by topical application. On the contrary, only analgesic effect was found in the syrupy residue. The significance of these pharmacological results was discussed.

著者

小山 岩雄 山上 治夫 桑江 豊保 倉田 宗司

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.102, no.8, pp.796-799, 1982

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The contents of 6-keto-prostaglandin F<SUB>1&alpha;</SUB> (6KF<SUB>1&alpha;</SUB>) and thromboxane B<SUB>2</SUB> (TXB<SUB>2</SUB>) in mouse peritoneal macrophages were determined by radioimmunoassay. When indomethacin at a final concentration of 0.1 mM was added at each stage in the preparation of macrophage samples, i.e. (I) before incubation of peritoneal exudate cells in glass dishes to prepare macrophage monolayers, (II) before harvest of macrophages from the glass surfaces, (III) before sonication of macrophage suspensions, and (IV) before centrifugation of sonicated macrophage solutions, large differences were detected in the contents of 6KF<SUB>1&alpha;</SUB> and TXB<SUB>2</SUB> at each stage. These results suggested that physical stimulation during the preparation of samples resulted in increases of 6KF<SUB>1&alpha;</SUB> and TXB<SUB>2</SUB> production by macrophages.

著者

岩出 賢太郎 下路 静佳 正木 秀典 酒井 隆全 田辺 公一 後藤 伸之 大津 史子

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

pp.18-00205, (Released:2018-12-05)

参考文献数

19

被引用文献数

1

---

We investigated the possibility that having pharmacists give asthma patients informational sheets on climate and environmental changes at insurance pharmacies during patient counseling might prevent the worsening of asthma symptoms. Patients with hyperlipidemia were comparative subjects. We created informational sheets about climate and environmental changes and their influence on asthma. During patient counseling, pharmacists gave them to all asthma patients who visited insurance pharmacies over a period of 2 months, between November and December 2017. Based on previous studies, we called days which showed certain climate or environmental changes as compared to the previous day “change days”. We compared the number of visiting patients on change days after preventative information was provided (between January and March 2018) with the number before information was provided (between January and March 2017). In addition, we compared those numbers with the number of patients who visited the target pharmacies between January and March 2016 in order to examine the influence of yearly climate change. The same procedure was used with hyperlipidemic patients. The number of visiting asthma patients after information was provided significantly decreased (5.1±2.1, p=0.03) compared with the number before information was provided, between January and March 2017 (6.1±2.8). The number of aforementioned visits compared to those between January and March 2016 also significantly decreased (p=0.01). Our results suggest that preventative information about climate and environmental changes provided by pharmacists during patient counseling might influence the number of asthma patient visits and prevent the exacerbation of their symptoms.

著者

原野 一誠

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.125, no.6, pp.469-489, 2005-06-01 (Released:2005-06-01)

参考文献数

55

被引用文献数

7 7

---

Chugaev reaction provides access to olefins from alcohols without rearrangement through pyrolysis of O-alkyl S-alkyl dithiocarbonates (xanthates) via cis elimination. Xanthates having no β-hydrogens undergo thione-to-thiol rearrangement to give S,S-dialkyl dithiocarbonates (thiolcarbonates). Based on these backgrounds, we intended to use the dithiolcarbonates as precursors of thiols. Xanthates could be converted to the corresponding dithiolcarbonates by Lewis-acid catalysis. Pyridine N-oxides and 4-dimethylaminopyridine also catalyzed the rearrangement reaction. On the other hand, O-(2-alkenyl) S-alkyl dithiocarbonates undergo [3,3]-sigmatropic rearrangement to give the allylically rearranged S-(2-alkenyl) S-alkyl dithiocarbonates. The homoallylic xanthates gave the corresponding dithiolcarbonates on heating with phenols. Pyrolysis of allylic dithiolcarbonates caused retro-ene type reaction to give the allylic sulfides in which allylic rearrangement also occurs. Coupling of these pericyclic reactions with intramolecular Diels-Alder reaction affords a one-pot synthetic method for the construction of hydroisobenzothiophenes. The mechanisms of the cascade and related reactions are demonstrated by location of the transition states using molecular orbital calculation method at various levels of theory involving density functional theory (DFT).

著者

山崎 正利 池並 通裕 来生 淳 油井 聡 安部 茂 水野 伝一

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.104, no.7, pp.p769-774, 1984-07

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The present study shows that some selected anti-cancer drugs induce tumor lysis in vitro in cooperation with phagocytic cells (drug-dependent cellular cytotoxicity ; DDCC) and that chemotherapeutic drugs augment the mediator-dependent killing activity of macrophages. Tumor cells pretreated with the drugs were susceptible to phagocytemediated killing. Tumor necrosis serum can also cooperate with some drugs in killing tumor cells. Moreover, some selected drugs can induce cytotoxic macrophages and the quantitative changes of phagocytes such as polymorphonuclear leukocytes. These results suggest that some anti-cancer drugs have the activities of inactivation of tumor cells and/or activation of host cells. Thus, tumor cells may be killed effectively in vivo by anti-cancer drugs through these mechanisms.