著者

加藤 洋美 吉井 美智子 小澤 光一郎

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.127, no.12, pp.2035-2044, 2007-12-01 (Released:2007-12-01)

参考文献数

12

被引用文献数

13 9

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In the present study, we tested three kinds of sleeping drugs, consisting mainly of triazolam, brotizolam, and flunitrazepam, to compare the drug efficacy of generic drugs with that of original drugs. After these drugs were administered orally to mice, drug efficacy was evaluated in terms of ambulation, onset time of sleep, and duration of sleep in the open field test. For all kinds of sleep-inducing drugs, the drug efficacy of most generic drugs is not necessarily equal to that of the original drug. The main reason for the difference appears to be due to differences in the rate of absorption of the main drug. Any other differences between an original drug and a generic drug are caused by drug additives, the crystal form of the main drug, the formulation, and so on. In this study, the formulation was not the reason for the differences because all of the drugs were pulverized in a mortar and had no special coating. The drug additives for all the drugs are listed and the drug efficacy compared. Unfortunately, the information was not sufficient to shed any light on the differences in drug efficacy. For effective drug therapy, more information on drug additives should be provided.

著者

古山 渓行

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.138, no.6, pp.731-742, 2018-06-01 (Released:2018-06-01)

参考文献数

44

被引用文献数

2

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The combination of several aromatic rings and/or heterocycles can induce novel functions. This phenomenon is observed in porphyrin derivatives, commonly found in hemoglobin, in the active sites of P-450, etc. The ability of these structures to interact strongly with visible light accounts for today's increased interest in the development of rationally designed porphyrinoid-based optical materials. In the pharmaceutical sciences, designing near-IR materials can be a challenge due to the high transparency of near-IR light in biological samples. Phthalocyanines (Pcs) are robust organic dyes that are absorbed in visible light. A theoretical investigation of molecular orbitals of Pcs has revealed that the introduction of a phosphorus(V) atom into a macrocyclic core leads to a narrower highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap. Following these studies, we found that certain types of Pc phosphorus(V) complexes display main absorptions beyond 1000 nm. Additionally, phosphorus(V) complexes with other azaporphyrinoids have been designed and synthesized via a relatively simple procedure. These complexes showed novel optical properties which are potentially useful in the pharmaceutical and material sciences. Furthermore, we have overcome the problem of organic radicals and antiaromatic compounds, which are generally considered to be unstable, by using a combination of serendipitous synthetic methodologies and spectroscopic techniques. These novel azaporphyrin compounds are robust and free from transition metals. They are relatively easy to synthesize and also exhibit predictable properties.

著者

長井 長義

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.74, pp.148-154, 1888-04-07

著者

井出 直仁 佐藤 誠太郎 澤口 和代

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.12, pp.1609-1614, 2019-12-01 (Released:2019-12-01)

参考文献数

24

被引用文献数

9

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It has been reported that the risk of acute kidney injury (AKI) is higher during treatment with vancomycin and piperacillin/tazobactam compared to use of vancomycin and cefepim or meropenem. We investigated the risk of AKI in patients receiving vancomycin and piperacillin/tazobactam versus those receiving vancomycin and meropenem or doripenem. The subjects were patients over 18 years old who received either vancomycin and piperacillin/tazobactam (V+P/T therapy) or vancomycin and carbapenems (meropenem or doripenem) (V+C therapy) for at least 48 h between 1 May 2013 and 28 February 2019. The primary endpoint was the incidence of AKI in patients receiving V+P/T or V+C therapy, while the secondary outcome was the timing of AKI in each group. The incidence of AKI was 33.3% (9/27) in patients receiving V+P/T therapy versus 9.1% (5/55) in those receiving V+C therapy, and its incidence was significantly higher with the former regimen (χ2=5.90, p=0.015). Multiple logistic regression analysis confirmed that V+P/T therapy was associated with an increased risk of AKI compared to V+C therapy (adjusted odds ratio: 5.05, 95% confidence interval: 1.46-17.5, p=0.01). The time to onset of AKI after initiation of treatment was not significantly different between patients receiving V+T/P or V+C therapy [median (interquartile range): 4 d (2-6 d) versus 7 d (3-10 d); p=0.282]. V+P/T therapy was associated with a significantly higher incidence of AKI than alternative regimens, suggesting that it should be avoided. When broad spectrum antibacterial therapy is required, V+C therapy should be considered instead.

著者

山梨 義英

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.12, pp.1485-1494, 2019-12-01 (Released:2019-12-01)

参考文献数

38

被引用文献数

2

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Several fat-soluble compounds such as cholesterol and fat-soluble vitamins have important physiological activities in the body, and their excess and/or deficiency have been reported to be closely associated with the onset and progression of several conditions such as lifestyle-related diseases. It is important to clarify not only the physiological activities but also in vivo kinetics of fat-soluble compounds to understand their in vivo activity (toxicity). This review introduces our recent (reverse) translational research in a combination of basic and clinical studies to reveal the regulatory mechanisms of in vivo behaviors of fat-soluble compounds and effects of their disruption in humans.

著者

高木 修造 山木 正枝 増田 京子 西浜 幸江 先名 淳

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.7, pp.657-659, 1981-07-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

8 11

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From Hedyotis corymbosa LAM., which has been recently used in chinese medicine as a useful drug against some tumors, were isolated six iridoids, asperuloside, scandoside methyl ester, asperulosidic acid, geniposidic acid, scandoside and deacetylasperulosidic acid.

著者

中舘 和彦 本島 健人 鎌田 純人 吉田 哲朗 疋田 真彬 若松 永憲

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.134, no.7, pp.829-838, 2014-07-01 (Released:2014-07-01)

参考文献数

24

被引用文献数

3 7

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Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice significantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, we observed eosin-negative accumulations of hepatocytes around central veins in the hepatic lobule. By Oil-Red O staining, the eosin-negative granules were identified in the lipid droplets. We then ascertained whether these lipid droplets of hepatocytes in the obese mice could be modified by diet. After 24 h of diet restriction, the lipid droplets of hepatocytes in the obese mice were swollen. Furthermore, after 48 h of the diet restriction, the lipid droplets continued swelling and the autophagy-like structures that were found in the healthy mice under the same condition in the obese mice were not observed. These results suggest that the obese mice might have delayed energy metabolism, which might have influenced the mechanisms of hepatocytes. These findings provide new insight into the functional changes in chronic obesity-induced type 2 diabetes and it is possible that the pathological feature make a contribution to promise the target of pharmacological therapy.

著者

生田 智樹 三浦 健 篠塚 和正

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.11, pp.1463-1470, 2019-11-01 (Released:2019-11-01)

参考文献数

27

被引用文献数

3

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Since “Foods with Function Claims” system was established in 2015, the percentage of people taking health foods and supplements is gradually increasing. The number of people taking both dietary supplements and medicines is also increasing. Therefore, providing information on interaction between dietary supplements and medicines has become increasingly important. We have conducted a study for understanding the awareness of the consumers on the interaction of health foods and supplements with medicines. The ratio of those who do not consult with an informed opinion on the interaction between health foods and supplements with medicines was 76% and 55.2% admitted that they did not experience any side effects as a result of this interaction. In conclusion, the understanding of the interaction between health foods and medication among consumers is still limited and most of them do not consult with specialized physicians. It has been revealed that efforts to expanding the consumers understanding on the risk of interaction between supplements and medicines are necessary. It was suggested that the “Database for guiding the interaction between medicines and health foods” could be a useful tool for providing this type of information.

著者

松浦 寿喜 吉川 友佳子 升井 洋至 佐野 満昭

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.124, no.4, pp.217-223, 2004-04-01 (Released:2004-03-27)

参考文献数

25

被引用文献数

17 22

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The inhibitory effects on the intestinal digestion and absorption of sugar of health teas that claim beneficial dietary and diabetes-controlling effects were compared in rats using portal cannulae. The measured durations were the times during which the elevation of portal glucose levels resulting from continuous intragastric infusion of sucrose or maltose was suppressed by concentrated teas. The teas investigated included salacia oblonga, mulberry, guava, gymunema, taheebo, yacon, and banaba. The duration of the inhibitory effect on the sucrose load of salacia oblonga, mulberry, and guava were 110 min, 20 min, and 10 min, respectively. In contrast, gymunema, taheebo, yacon, and banaba had no significant effect on the continuous infusion of sucrose. These results suggest that there is considerable difference in the efficacy of commercial health teas in influencing glucose absorption.

著者

有富 正和

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.82, no.5, pp.771-773, 1962-05-25 (Released:2010-02-19)

参考文献数

12

被引用文献数

1 3

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Astragalin was isolated and identified from the flower petals of Rosa multiflora THUNB. Astragalin and trifolin were separated and identified from the flower petals of Rubus hirsutus THUMB.

著者

正山 征洋

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.10, pp.1593-1620, 2007-10-01 (Released:2007-10-01)

参考文献数

92

被引用文献数

4 4

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In order to quality control for medicinal plants such as Aconitum charmicaelii, Rhemannia glutinosa, Atractyrodes lancea, Pinellia ternata, Panax species and Gentiana scabra were clonally micropropagated by tip tissue culture and embryogenetic techniques. Monoclonal antibodies against the bioactive compounds contained in the crude drugs were prepared and set up the ELISA as a high sensitive and quick determination method. A newly developed eastern blotting methodology can stain typically the only antigen molecule and the related compounds having a same aglycone. Knockout extract can be prepared by using an immunoaffinity column conjugated with monoclonal antibody, and its importance has been discussed. Single chain fragment-variable gene against solamargine was cloned and transformed to a host plant, Solanum chasianum resulting in the increase of antigen molecule as 2.5 to 3 times. Three biosynthetic enzymes regarding marihuana compounds, THCA-, CBDA-, CBCA-synthases were isolated. THCAsynthase was cloned, over expressed and confirmed its characteristics including FAD combining enzyme, and finally determined the structure by X-ray analysis. The distribution of THCAsynthase was also investigated using its and GFP hybrid gene. We found new functions for saffron like improving learning and memory and LTP for blocking by ethanol. A folk medicine in Taiwan, Anoectochilus formosanus was propagated in vitro and investigated opening new pharmacological activities in lipid methabolism.

著者

北 泰行

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.122, no.12, pp.1011-1035, 2002-12-01 (Released:2003-02-18)

参考文献数

109

被引用文献数

13 17

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Biologically active natural products with unique, highly complex molecular skeletons have been used as leading compounds for raw materials of new drugs. Due to the limitations of natural supply, highly efficient, large-scale syntheses and molecular design have been sought in drug discovery. For this purpose, we have focused on a synthetic strategy effective in developing novel reactions and reagents and found several useful regio- and stereospecific reactions, contributing to the synthesis of otherwise unattainable target molecules. The application of these reactions for the total synthesis of three types of potent cytotoxic natural products for the first time is described in this paper. The basic concept is first described. Then the total synthesis of anthracyclines, fredericamycin A, and discorhabdins is reported. Novel reactions using hypervalent iodine reagents under environmentally benign conditions are also described. The future prospects for this method are discussed.

著者

矢野 育子

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.139, no.10, pp.1227-1234, 2019-10-01 (Released:2019-10-01)

参考文献数

31

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Pharmacometrics is the mathematical study of pharmacokinetics, disease progression, and clinical outcomes. One objective of pharmacometrics is to facilitate rational drug treatment in patients, also termed clinical pharmacometrics. In this review, our clinical pharmacometric studies conducted over the last 10 years are discussed. Population pharmacokinetic analysis using therapeutic monitoring data for levetiracetam revealed that oral clearance allometrically scaled to both body weight and estimated glomerular filtration rate can accurately predict clinical data from patients of various ages (pediatric to elderly) with varying renal function. Dosage adjustments based on renal function in the package information are effective in controlling the trough and peak concentrations in similar ranges. In addition, a retrospective pharmacokinetic and pharmacodynamic study revealed that the efficacy of low-dose clobazam therapy was significantly influenced by CYP2C19 polymorphisms. Pharmacokinetic and pharmacodynamic models were successfully built using electronic medical information to explain retrospective international normalized ratio values of prothrombin time before and after catheter ablation in warfarin-treated patients. Simulation studies suggest that more than 20 mg of vitamin K2 is unnecessary in the preoperative period of catheter ablation. A physiologically based pharmacokinetic model adapted to tacrolimus pharmacokinetic data in patients who underwent living-donor liver transplantation was constructed, and clarified that oral clearance of this drug was affected by CYP3A5 genotypes in both the liver and intestine to the same extent. In conclusion, pharmacometrics is a useful methodology for individualized and optimized drug therapy.

著者

恩田 光子 高垣 伸匡

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.5, pp.645-647, 2018-05-01 (Released:2018-05-01)

参考文献数

3

被引用文献数

3

---

Osaka University of Pharmaceutical Sciences has included an evidence-based medicine (EBM) exercise in the introductory education for clinical practice for 4th-year pharmacy students since 2015. The purpose of this exercise is to learn the process of practice and basic concepts of EBM, especially to cultivate the practical ability to solve patients' problems and answer their questions. Additionally, in 2016, we have attempted flipped teaching. The students are instructed to review the basic knowledge necessary for active learning in this exercise by watching video teaching materials and to bring reports summarizing the contents on the flipped teaching days. The program includes short lectures [overview of EBM, document retrieval, randomized controlled trials (RCTs), and systematic review], exercises [patient, intervention, comparison, outcome (PICO) structuring, critical appraisal of papers in small groups with tutors], and presentations. The program includes: step 1, PICO structuring based on scenarios; step 2, critical appraisal of English-language papers on RCTs using evaluation worksheets; and step 3, reviewing the results of the PICO exercise with patients. The results of the review are shared among groups through general discussion. In this symposium, I discuss students' attitudes, the effectiveness of small group discussions using flipped teaching, and future challenges to be addressed in this program.

著者

清水 忠 安原 智久

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.5, pp.629, 2018-05-01 (Released:2018-05-01)

著者

金子 雅幸

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.6, pp.805-809, 2016-06-01 (Released:2016-06-01)

参考文献数

26

被引用文献数

2 6

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Studies on endoplasmic reticulum (ER)-associated degradation (ERAD), in which unfolded proteins accumulated in the ER are selectively transported to the cytosol for degradation by the ubiquitin-proteasome system, have been focused on molecular mechanisms in yeast. In human, disruption of the ER quality control system causes various diseases, such as neurodegenerative disease, lifestyle disease, and cancer. However, there are many ERAD genes with unknown physiological and pathological functions. We identified the novel ubiquitin ligase HRD1 involved in ERAD. HRD1 is expressed in brain neurons and protects against ER stress-induced apoptosis. In familial Parkinson's disease, accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of ubiquitin ligase Parkin involved in ERAD, causes ER stress and apoptosis. We demonstrated that HRD1 promotes ubiquitination and degradation of Pael-R and suppresses ER stress and apoptosis induced by Pael-R. Amyloid precursor protein (APP) is processed into amyloid β (Aβ) in Alzheimer's disease. We found that HRD1 promotes APP ubiquitination and degradation, resulting in decreased generation of Aβ. Furthermore, suppression of HRD1 expression causes APP accumulation and Aβ generation associated with ER stress and apoptosis. Interestingly, HRD1 protein levels significantly decreased in the cerebral cortex of Alzheimer's disease patients, possibly because of its insolubilization. We demonstrated that HRD1 protein was insolubilized by oxidative stress, resulting in the accumulation of HRD1 into the aggresome. In conclusion, oxidative stress-induced HRD1 insolubilization might be involved in a vicious cycle of increased Aβ production and Aβ-induced oxidative stress in Alzheimer's disease pathogenesis.

著者

澁谷 正俊

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.10, pp.1131-1143, 2012-10-01 (Released:2012-10-01)

参考文献数

55

被引用文献数

2 4

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Organic nitroxyl radical catalysts have recently attracted great attention because they realize efficient alcohol oxidation under mild and environmentally benign conditions. A representative of this class is 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO). We have also developed 2-azaadamantane N-oxyls (AZADOs) as highly efficient oxidation catalysts. These nitroxyl radicals are generally oxidized by a cooxidant to generate oxoammonium salts, which are active species for alcohol oxidation. In the oxidation systems presented in this paper, we focus on the differences between these two species in terms of oxidation state and counter anion. Herein, the effects of a counter anion of an oxoammonium species on its reaction selectivity are shown. On the basis of the control of the counter anion, we have developed catalytic oxidative rearrangement of tertiary allylic alcohols to β-substituted α,β-unsaturated carbonyl compounds. Moreover, we have developed novel useful oxidation systems utilizing a catalytic oxoammonium salt; namely, a one-pot oxidation of primary alcohols to carboxylic acids and an aerobic alcohol oxidation.

著者

中川 俊夫 森 芳夫

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.75, no.11, pp.1322-1325, 1955-11-25 (Released:2010-02-19)

参考文献数

7

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Water-soluble vitamin E derivative was obtained by the reaction of α-tocopheryl dichlorophosphate and polyethylene glycol. The reaction product was purified through alumina chromatography and from the phosphorus content, ultraviolet and infrared absorption, average molecular weight, and the hydrolyzates, the product was assumed to be a mixed phosphate of α-tocopherol and polyethyleneglycol.

著者

川谷 豊彦 藤田 早苗之助 大野 忠郎 久保木 憲人

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.78, no.1, pp.58-61, 1958-01-25 (Released:2010-02-19)

参考文献数

6

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1) It was found that the cultivation of Ammi visnaga LAM. in Japan should start with autumn sowing during the middle of October, at the latest, from the point of growth, yield of fruit, and content of khellin (Table I).2) The optimal soil moisture in the said cultivation seems to be in the range of 60-70% of the water capacity from the point of growth, yield of fruit, and khellin content (Table II).3) This plant grows favorably in the soil with pH ranging from 6.5 to 7.5, with neutral reaction as the median point.4) It was confirmed through experimental cultivation extending from 1951 to 1955 that the cultivation of this plant should be made in a place with small amount of rainfall during the summer and a well-drained soil rich in clay (Tables II and III).5) Comparative cultivation was carried out with five foreign strains with different origin (khellin content of the original seed, 0.61-0.94%) and the khellin content of the fruit from these cultivated plants was 0.32-0.51%, indicating a fair decrease of the content. However, this was thought to be due to the profuse generation of diseases during August, before flowering, and unhealthy fruit had been mixed (Table IV).6) In one individual plant, the fruits that ripened earlier seemed to have higher content of khellin (Table V).

著者

篠田 雅人 高木 良成 玉置 文一

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.86, no.4, pp.306-314, 1966

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Anti-saliva Parotin-A serum was obtained after the administration of saliva Parotin-A (SPA) to intact rabbits in the following doses : 10 μg./kg. for 10 days, 100 μg./kg. on the 11th day, 1 mg. on the 42nd day, and 2 mg. on the 54th day. By the technique of Ouchterlony, the antiserum obtained showed a precipitin band against SPA, but was not reactive to Parotin, S-Parotin, α-Uroparotin, β-Uroparotin, lyophylized saliva, etc., showing immunological specificity of the antiserum. The quantitative precipitin tests indicated that 1 ml. of the antiserum corresponded to 300 μg. of SPA. Administration of SPA mixed with the antiserum was found to be as effective as SPA alone upon the circulating leucocytes, while the antiserum itself showed no significant influence upon them. After mixing SPA with the antiserum in a ratio which ensured complete precipitation of SPA, the precipitate as well as the supernatant showed leucocyte-promoting activitiy. Besides this activity, the precipitate reduced the circulating lymphocytes, while the supernatant increased the granulocytes more markedly. These results suggest that the SPA used in this study contained at least two components ; one was precipitated by the antiserum and, after precipitation, still retained its leucocyte-promoting activity and the other was not precipitated. It was also found that the antigenic center of SPA would be different from the leucocyte-promoting activity in the molecules.