著者

角 保男

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.81, no.5, pp.652-655, 1961-05-25 (Released:2010-02-19)

参考文献数

5

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Leucoriboflavin 5′-phosphate derivatives were prepared by reductive acylation of riboflavin 5′-phosphate. These compounds were rather unstable and were easily hydrolyzed to riboflavin 5′-phosphate derivatives, regaining the yellow color. On heating with 17% hydrochloric acid, leucoriboflavin 5′-phosphate tetraacetate and monoethylformate yielded riboflavin 2′, 5′-anhydride, m.p. 300-302°. This substance was sensitive to light and formed lumichrome as the photo-decomposition product on exposure to light.

著者

角 保男

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.81, no.5, pp.647-651, 1961-05-25 (Released:2010-02-19)

参考文献数

3

---

Leucoriboflavin, reduced form of riboflavin, is easily oxidized to riboflavin when shaken with air. To retain the leuco state, riboflavin was reduced with sodium dithionite or with zinc in acid solution to the leuco compound and its acylation with acetic anhydride or benzoyl chloride gave leucoriboflavin acylate. These compounds were stable in solid state but were easily decomposed to riboflavin acylate on exposure to sunlight or by heating, regaining the yellow color. Several decomposition products of leucoriboflavin acylate are described.

著者

立浪 良介 高橋 恭兵 大場 達也 丹保 好子

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

vol.129, no.1, pp.147-153, 2009 (Released:2009-01-01)

参考文献数

32

被引用文献数

2 6

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Methylglyoxal (MG), a highly reactive dicarbonyl compound, is a metabolic by-product of glycolysis. MG is often detected at high levels in the blood of diabetic patients. We examined whether MG was capable of inducing reactive oxygen species (ROS) production in bovine aortic endothelial cells (BAECs). The viability of BAECs decreased with time on treatment with 5 mM MG, and was almost completely lost at 24 h. In contrast, MG at 1 mM had little influence on BAEC viability up to 24 h, but induced the elevation of intracellular glutathione content at 24 h. Exposure of BAECs to MG caused a dose-dependent increase in oxidized-hydroethidine fluorescence intensity, indicating ROS production. In addition, aconitase inactivation, which is an indicator of intracellular superoxide, was observed in MG-treated cells. Finally, we found that MG at 5 mM increased the fluorescence intensity of BES-So, a specific probe for superoxide. Together, the results suggest that MG induces superoxide production in endothelial cells, and that the accumulation of ROS may be linked to cytotoxic effects.

著者

樽井 敦

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.135, no.11, pp.1245-1253, 2015 (Released:2015-11-01)

参考文献数

51

被引用文献数

2

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Multi-substituted β-lactam compounds have not only attracted considerable interest as core structures of pharmaceutical compounds such as antibiotics but also have been used as building blocks for the construction of β-amino acids. Electrophilic β-lactams can be used to enhance essential biological activities. Furthermore, the ring-opening reactions of electrophilic β-lactams can be used to provide facile access to β-amino acids. The introduction of an electronegative fluorine atom to a β-lactam ring to give the corresponding fluoro-β-lactam can be used as an effective strategy for the preparation of electrophilic β-lactams. In this review, we provide a summary of our recent research towards the direct functionalization of fluoro-β-lactams. This review has been divided into four topics, including: 1) the alkylation and hydroxyalkylation of α-bromo-α-fluoro-β-lactams (1); 2) the nickel-catalyzed cross coupling reaction of 1; 3) the asymmetric synthesis of fluoro-β-lactams using chiral ligands; and 4) the utilization of fluoro-β-lactams as highly electrophilic building blocks.

著者

水田 博彰 鮫元 博文 小川 建志

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.8, pp.445-450, 1991-08-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

1 1

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The effects of triglycerides on the gastrointestinal absorption of 2-[3-(3, 5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo [3, 4-b] pyridin-1-yl] ethyl acetate (1) were investigated in dogs. The enhancing abilities of the triglycerides on the absorption of 1 were demonstrated as in the order of trilinolein>triolein>tristearin>tripalmitin. Among the series of fatty acids and monoglycerides, namely, digestive products of triglycerides by pancreatic lipase, linoleic acid and monolinolein showed the most potent solubilizing activities of 1 in a solution of bile salt. The incorporation of 1 into mixed micelle formed by lipids and bile salts was presumed to play an important role in the accelerated absorption of 1 after ingestion of triglycerides. On the basis of these findings, an emulsion containing 1 was prepared with soybean oil. The emulsion exhibited a remarkable improvement of the absorption of 1 compared to a suspension of the drug in methylcellulose solution.

著者

小菅 卓夫 神谷 弘子 足立 太平

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.82, no.1, pp.190-190, 1962-01-25 (Released:2010-02-19)

参考文献数

3

被引用文献数

10

著者

戸口 始 小川 泰亮 岡田 弘晃 山本 眞樹

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.8, pp.397-409, 1991-08-25 (Released:2008-05-30)

参考文献数

61

被引用文献数

10 14

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Leuprorelin (leuprolide, D-Leu6-(des-Gly10-NH2)-LH-RH ethylamide) acetate is a superactive agonist of luteinizing hormone-releasing hormone (LH-RH). We developed once-a-month injectable microcapsules of this agonist by our novel in-water drying method. This depot formulation can release the drug at an apparent zero-order rate over one month with bioerosion of copoly (lactic/glycolic acid) utilized as a wall material of the polycore microcapsules. A dramatic prolonged depression of pituitary-gonadal axis, chemical castration, was achieved by the once-a-month injection in experimental animals ; it expects a reliable effcacy for treating hormone-dependent prostatic, breast cancers and endometriosis. Studies on the dosage design of this new delivery system of leuprorelin are summarized.

著者

山口 智子 向井 志乃 魚谷 茂雄 大谷 壽一 澤田 康文

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.5, pp.331-338, 2002 (Released:2003-02-18)

参考文献数

10

被引用文献数

1

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Phenytoin (PHT) exhibits nonlinear pharmacokinetics in the therapeutic range. Therefore a slight increase in dose may lead to considerable elevation of the serum PHT level. Although its bioavailability is dependent on the formulation, bioequivalence is considered to be preserved between the three major formulations, of tablet, 97% fine granules, and 10% powder. However, we experienced many cases of increases serum PHT concentration after changes in formulation from 97% fine granules to 97/4% hospital-made fine granules, and from the latter to 10% powder. Retrospective analysis revealed that these alterations were accompanied by 55% and 16% increases in the serum concentration-to-dose ratio of PHT, respectively. We investigated the factors of this increase by analyzing the weight of remaining powder in a package and the PHT content of each formulation. Each package of PHT formulation prepared with 97% fine granules and 10% powder was unsealed, and the contents were weighed to calculate the rate of recovery. The rate of ingestion was estimated by correcting the rate of recovery by PHT strength (i. e., 1.0 for 10% powder and 0.97 for fine granules). The rates of recovery and ingestion for 10% powder were 13% and 16% higher than those for 97% fine granules, respectively (p<0.01). In conclusion, Changing the PHT formulation from 97% fine granules to 10% powder may lead to a considerable increase in the serum PHT concentration and possibly induce PHT toxicity.

著者

野田 幸裕 鍋島 俊隆

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.120, no.8, pp.677-682, 2000-08-01 (Released:2008-05-30)

参考文献数

24

被引用文献数

1 9

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To develop an animal model for negative symptoms, in particular avolition, of schizophrenia, the effect of phencyclidine (PCP) on immobility (regarded as avolition) in the forced swimming test was investigated in mice, since PCP produces negative symptoms in humans. Unlike single, repeated treatment with PCP prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment. The enhancing effect of PCP on the immobility persisted for 21 d after the withdrawal of the drug. Atypical antipsychotics attenuated the enhancing effect of PCP on the immobility. Since these attenuating effects were antagonized by a serotonin-S2 receptor agonist, (±)-2, 5-dimethoxy-4-iodamphetamine (DOI), the effects may be mediated via serotonin-S2 receptors. In contrast with atypical antipsychotics, typical antipsychotics, antidepressants and anxiolytics had no effect. No functional changes in post-synaptic serotonin-S2 reseptors were observed in PCP-treated mice following the forced swimming test. Serotonin utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in PCP-treated mice showing the enhancement of immobility. The enhancing effect of PCP was significantly attenuated by D-cycloserine, an agonist for glycine binding site of N-methyl-D-aspartate (NMDA) receptor ionophore complex. Decreases of NMDA receptor function or of the cortical glutamate and glycine levels were observed in PCP-treated mice showing the enhancement of immobility. These results suggest that the enhancing effect of PCP on immobility is mediated by the imbalance of the cortical serotonergic, dopaminergic and glutamatergic systems and could be used as an animal model for negative symptoms of schizophrenia.

著者

杉本 八郎

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.130, no.4, pp.521-526, 2010 (Released:2010-04-01)

参考文献数

8

被引用文献数

6 6

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Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. However, these drugs do not cure Alzheimer's, but are only symptomatic treatments. Therefore, a cure for Alzheimer's disease is truly needed. Alzheimer's disease is a progressive neurodegenerative disease characterized by cognitive deficits. The cause of the disease is not well understood, but research indicates that the aggregation of β-amyloid is the fundamental cause. This theory suggests that β-amyloid aggregation causes neurotoxicity. Therefore, development of the next anti-Alzheimer's disease drug is based on the β-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.

著者

岡﨑 敬之介 渡邊 徹 齋藤 勲 村山 純一郎

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.132, no.2, pp.231-236, 2012 (Released:2012-02-01)

参考文献数

10

被引用文献数

2 2

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Our aim was to clarify the side effects of irinotecan which occurred in patients admitted to Showa University Hospital to investigate whether the UGT1A1 genetic polymorphism status was reflected in the discontinuation or dose reduction of irinotecan. We retrospectively investigated UGT1A1 genetic polymorphisms, irinotecan dosage, dose discontinuance or reduction, and laboratory results from May 1 2009 to April 30 2010. The analysis of UGT1A1 genetic polymorphisms in 23 patients showed that frequencies of the UGT1A1*6 and UGT1A1*28 polymorphisms were 35% (eight patients) and 22% (five patients), respectively, and 17% (three patients) were UGT1A1*6/UGT1A1*28 compound heterozygotes. Of all patients who received irinotecan, dose reduction occurred in six patients (38%) and discontinuance in two patients (13%) due to neutropenia and other factors. Of these eight patients, seven (88%) had the UGT1A1*6 and/or *28 polymorphism. The most common irinotecan dose reduction was about 25% of the initial dose. Grade 4 neutropenia was observed in two patients who had the UGT1A1*6 and/or *28 mutation (13%), and one patient was a compound heterozygote. Our investigation confirmed that the UGT1A1 genetic polymorphism status of the patients was reflected in the discontinuance or dose reduction of irinotecan. Our results suggest that Grade 4 neutropenia may occur in patients who are compound heterozygotes and that these patients may need careful selection of treatment regimens possibly involving discontinuance or reduction in irinotecan dosage.

著者

富松 利明 松井 又夫 宇治 昭 加納 蓉子

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

vol.82, no.11, pp.1560-1563, 1962-11-25 (Released:2010-02-19)

参考文献数

5

被引用文献数

6

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Experimental evidences suggest that the bases contained in Thalictrum thunbergii DC. (Japanese name “Akikaramatsu”) differs slightly by its habitat. In order to elucidate this point, the root of this plant collected in Nagano Prefecture was processed and a comparatively large amount of magnoflorine (I) was obtained, while its leaves and stems yielded takatonine (II). The leaves and stems of the same plant collected in Kochi Prefecture yielded magnoflorine (I) and berberine (III). These results are summarized in Table I.

著者

佐井 君江 澤田 純一 南 博信

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.4, pp.575-584, 2008 (Released:2008-04-01)

参考文献数

42

被引用文献数

10 19

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Recent progress in pharmacogenetic research has made “personalized medicine” a reality, where a suitable drug at the appropriate dosage is prescribed based on individual genetic factors. Irinotecan, an anticancer drug, is one of the models for personalized medicine, and a number of clinical studies have revealed significant associations between UGT1A1*28 and irinotecan toxicity. Based on the cumulative evidence, clinical tests for the UGT1A1*28 marker have started in the United States since 2005. However, the appropriate criteria for irinotecan dose adjustments have not yet been fully established. Since there are considerable differences in genetic polymorphisms among different ethnic groups and in approved irinotecan-containing regimens between countries, the criteria for the choice of suitable genetic markers and dose adjustments should be standardized in each country. This mini-review outlines our recent studies on irinotecan pharmacogenetics and discusses the clinical significance of UGT1A1*6 and *28 markers for personalized irinotecan therapy in Japanese cancer patients.

著者

林 恭子 大津 史子 矢野 玲子 榊原 仁作 後藤 伸之

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.131, no.1, pp.139-152, 2011 (Released:2011-01-01)

参考文献数

32

被引用文献数

3 3

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The present study investigated risk factors and subjective symptoms associated with drug-induced leucopenia. We selected 248 patients with drug-induced leucopenia from the Case Reports of Adverse Drug Reactions and Poisoning Information System (CARPIS) database of over 47000 case reports of adverse drug reactions and assigned them to a case group. We also randomly selected 743 cases of adverse drug reactions not associated with leucopenia as a control group. A comparison of patient characteristic data between the two groups using logistic-regression analysis revealed that female sex, autoimmune disease and renal damage were background risk factors for drug-induced leucopenia. In addition, thiamazole, ritodrine, propylthiouracil, ticlopidine, allopurinol, minocycline and captopril administration significantly increased the risk of drug-induced leucopenia. A significant association was also found for fever, chills and pharyngeal abnormalities. Based on these findings, we developed two estimated regression equations to help prevent drug-induced leucopenia in the community pharmacy setting.

著者

菅谷 幸子 吉葉 孝子 梶間 隆 石濱 泰

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.237-246, 2002 (Released:2003-02-18)

参考文献数

15

被引用文献数

12 21

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We developed two methods for solubility screening of drug candidates in drug discovery. The first is a solution-precipitation (SP) method, in which the sample solutions are prepared by adding the drug solution in dimethylsulfoxide (DMSO) to buffers followed by filtering off the precipitate using 96-well filterplate. The second is a powder-dissolution (PD) method, in which the solid samples are dissolved to the buffer in the HPLC vial equipped with the filter membrane in the HPLC autosampler. An HPLC equipped with a photodiode array detector is used to measure the concentration of the sample solutions in both methods. The SP method was used for high throughput screening the solvating process of the candidates in aqueous solutions with lower sample consumption, and the PD method was used for screening both inter-molecular interaction in solid state and solvation in aqueous solution with more sample amount than that of SP method. Therefore, the solubility screening from early to final stage of lead optimization process would be successfully accomplished by using both methods complementarily.

著者

潮平 英郎 仲松 正司 喜瀬 勇也 比嘉 太 健山 正男 外間 惟夫 国吉 幸男 植田 真一郎 中村 克徳 藤田 次郎

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.136, no.9, pp.1313-1317, 2016 (Released:2016-09-01)

参考文献数

16

被引用文献数

1 2

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Teicoplanin, a glycopeptide antibiotic for methicillin-resistant Staphylococcus aureus, is recommended for therapeutic drug monitoring during treatment. Maintaining a high trough range of teicoplanin is also recommended for severe infectious disease. However, the optimal dose and interval of treatment for severe renal impairment is unknown. We report a 79-year-old man who received long-term teicoplanin treatment for methicillin-resistant Staphylococcus aureus bacteremia due to postoperative sternal osteomyelitis with renal impairment. Plasma teicoplanin trough levels were maintained at a high range (20-30 μg/mL). Although the patient required long-term teicoplanin treatment, a further decline in renal function was not observed, and blood culture remained negative after the start of treatment. Teicoplanin treatment that is maintained at a high trough level by therapeutic drug monitoring might be beneficial for severe methicillin-resistant Staphylococcus aureus infection accompanied by renal impairment.

著者

香川 靖雄

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.107, no.11, pp.835-848, 1987-11-25 (Released:2008-05-30)

参考文献数

38

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Adenosinetriphosphate (ATP) synthase (FoF1) is a major energy supplying enzyme of cells utilizing the proton motive force. It consists of a catalytic portion called F1 and a proton channel portion called Fo. In order to elucidate the chemical reaction of FoF1, thermophilic FoF1 (TFoF1) was used, because it is stable and could eb reconstituted without Mg-ATP. In contrast to the previous hypotheses on the ATP synthesis, direct measurement of H+ current through TFoF1 incorporated into a planar lipid bilayer, 3H+/ATP stoichiometry was obtained. The primary structure of TFoF1 was established by sequencing its operon deoxyribonucleic acid and subunit peptides. The stereochemistry of the reaction using [16O, 17O, 15O, 35S] thiophosphate supported the a pathway for associative nucleophilic displacement on a phosphoric ester without pseudorotation. The diastereoisomeric preference of Cd-ATPγS revealed that the true substrate of TFoF1 is Δ, β, γ, bidentate Mg-ATP, like adenylate kinase. The site directed mutagenesis of the residues of F1 homologous to Mg-ATP binding site of adenylate kinase revealed their essential role in the reaction. Mitchell's chemiosmotic theory was refined by these results.

著者

畝山 寿之 竹内 孝治

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.1675-1676, 2011 (Released:2011-12-01)

参考文献数

8

著者

岡崎 研太郎

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.135, no.3, pp.351-355, 2015 (Released:2015-03-01)

参考文献数

8

---

The empowerment approach to patients with diabetes is a philosophy that was introduced by Robert M. Anderson and Martha M. Funnell of Michigan Diabetes Research and Training Center in the 1990s. This approach is based on the observation that more than 98% of diabetes care is performed by patients themselves. Dr. Anderson, Ms. Funnell, and their colleagues found that every patient has a right and an ability to solve his/her own problem in his/her own diabetes. Therefore healthcare providers should provide support for patients own endeavors. Empowerment has three essential elements: 1) the patient is centered, they make a final decision of their daily self-management, and are responsible for those decisions and the results; 2) patient support is the main role of healthcare providers; and 3) patient and healthcare providers should collaborate. In this author's opinion, it is important for healthcare providers to improve their communication skills to use the empowerment approach to help patients change their behaviors in the real world. To encourage empowerment, we created a unique learning program for healthcare providers, named “Diabetes Theater”. This program is an interactive workshop comprising two parts: drama and discussion.

著者

佐々木 俊則 大島 有美子 三島 江津子 伴 晶子 桂川 健司 永松 秀紹 吉岡 祐貴 築山 郁人 久田 達也 板倉 由縁 水谷 三浩

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.7, pp.1023-1029, 2016 (Released:2016-07-01)

参考文献数

15

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It is often necessary to modify the dose or schedule of eribulin mesilate (Eri) because of adverse events. Therefore, we retrospectively investigated the optimal approach for Eri dose adjustment and/or dosage interval adjustment. Patients who received Eri at the institutions affiliated with the Division of Oncology of the Aichi Prefectural Society of Hospital Pharmacists between July 2011 and November 2013 were enrolled in this study. We compared the group that underwent dose reduction without changes to their dosage interval (dose reduction group) with the group that had a change in their dosage interval (dose-interval prolongation group). The primary end-point was time to treatment failure (TTF), and the secondary end-points were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and adverse events. The TTF and OS of the dose reduction group were approximately two times longer than those of the dose-interval prolongation group. In addition, the dose reduction group had significantly improved ORR and CBR, which together indicate an antitumor effect (p=0.013 and 0.002, respectively). Although peripheral neuropathy occurred significantly more frequently in the patients in the dose reduction group (p=0.026), it was grade 1 and controllable in most of the cases. There were no differences in the occurrence of other adverse effects between the two groups. Therefore, we suggest that dose reduction with maintenance of the dosage interval is the preferred treatment approach in cases where Eri dose or schedule modification is necessary.