著者

Kenichi Kawano Fumiaki Yokoyama Kouhei Kamasaka Jun Kawamoto Takuya Ogawa Tatsuo Kurihara Shiroh Futaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.11, pp.1075-1082, 2021-11-01 (Released:2021-11-01)

参考文献数

38

被引用文献数

4

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Extracellular vesicles (EVs) have emerged as important targets in biological and medical studies because they are involved in diverse human diseases and bacterial pathogenesis. Although antibodies targeting the surface biomarkers are widely used to detect EVs, peptide-based curvature sensors are currently attracting an attention as a novel tool for marker-free EV detection techniques. We have previously created a curvature-sensing peptide, FAAV and applied it to develop a simple and rapid method for detection of bacterial EVs in cultured media. The method utilized the fluorescence/Förster resonance energy transfer (FRET) phenomenon to achieve the high sensitivity to changes in the EV amount. In the present study, to develop a practical and easy-to-use approach that can detect bacterial EVs by peptides alone, we designed novel curvature-sensing peptides, N-terminus-substituted FAAV (nFAAV) peptides. The nFAAV peptides exerted higher α-helix-stabilizing effects than FAAV upon binding to vesicles while maintaining a random coil structure in aqueous solution. One of the nFAAV peptides showed a superior binding affinity for bacterial EVs and detected changes in the EV amount with 5-fold higher sensitivity than FAAV even in the presence of the EV-secretory bacterial cells. We named nFAAV5, which exhibited the high ability to detect bacterial EVs, as an EV-sensing peptide. Our finding is that the coil–α-helix structural transition of the nFAAV peptides serve as a key structural factor for highly sensitive detection of bacterial EVs.

著者

Toshinori Hirai Chihiro Shiraishi Tomohiro Murata Takuya Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.4, no.5, pp.170-174, 2021 (Released:2021-10-28)

参考文献数

24

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The impact of renal impairment on the drug-drug interaction between azathioprine and allopurinol that causes myelosuppression and hepatotoxicity remains unclear. This case series study investigated adverse effects caused by azathioprine owing to drug-drug interaction considering renal impairment. Patients who started the combination therapy of azathioprine and allopurinol at Mie University Hospital between January 2013 and February 2021 were enrolled. The outcome of adverse events associated with azathioprine was assessed according to Common Terminology Criteria for Adverse Events version 5.0. The Drug Interaction Probability Scale was used to determine the probability of drug-drug interaction. Of the three patients, two were identified as exhibiting drug-drug interaction with the Drug Interaction Probability Scale > 5 points. They experienced grade 3 myelosuppression or hepatotoxicity with fatigue, after initiation of azathioprine (1.28 and 0.44 mg/kg once daily) and allopurinol (50 mg once daily). They received appropriate dose-adjusted allopurinol according to renal function. Additionally, both patients had the estimated glomerular filtration rate < 60 mL/min/1.73 m2. Thus, renal impairment might reduce the excretion of oxypurinol, an active metabolite of allopurinol, which certainly enhances the side effects of azathioprine.

著者

Fumihiro Nishimura Tomoko Ushijima Masako Nojima Shinsuke Hamada Kazumasa Hara Yasuyuki Hamada Daisuke Kadowaki Shigeyuki Miyamura Kentaro Oniki Junji Saruwatari

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1427-1432, 2021-10-01 (Released:2021-10-01)

参考文献数

27

被引用文献数

3

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Non-steroidal anti-inflammatory medications are associated with renal impairment. However, there is little information on whether these medications affect postoperative renal function compared with acetaminophen. The objective of this study was to compare the effects of acetaminophen and loxoprofen, used as postoperative analgesic, effect on postoperative analgesia using propensity score matching analysis. We retrospectively enrolled 328 patients treated with loxoprofen or acetaminophen after open radical prostatectomy between October 2017 and February 2020. We analyzed postoperative pain intensity, the incidence rate of acute kidney injury, drug-induced liver injury, and rate of elevation in serum creatinine after open radical prostatectomy. Eighty-one matched pairs of patients treated with loxoprofen or acetaminophen were selected using propensity score matching analysis. The postoperative numerical rating scale was significantly higher in the acetaminophen group than in the loxoprofen group on postoperative day 5. The use of patient-controlled anesthesia and rescue analgesics was significantly higher in the acetaminophen group than in the loxoprofen group. The loxoprofen group had a significantly higher postoperative increase in serum creatinine than the acetaminophen group on postoperative days 5 and 8. The incidence of acute kidney injury was 4.9% in the loxoprofen group and 0% in the acetaminophen group, while the incidence of drug-induced liver injury was 0% in both groups. Acetaminophen appears to be safer than loxoprofen in terms of effects on renal function. Nevertheless, the number of acetaminophen doses and the dose per dose may need to be increased for patients with significant postoperative pain.

著者

Ryohei Aoyagi Takahiro Yamamoto Yuuki Furukawa Makoto Arita

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.10, pp.953-961, 2021-10-01 (Released:2021-10-01)

参考文献数

99

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Polyunsaturated fatty acids (PUFAs), esterified to phospholipids, are susceptible to oxidation. They form oxidized phospholipids (OxPLs) by oxygenases or reactive oxygen species (ROS), or both. These OxPLs are associated with various diseases, such as atherosclerosis, pulmonary injuries, neurodegenerative diseases, cancer, and diabetes. Since many types of OxPLs seem to be generated in vivo, precise determination of their structural diversity is required to understand their potential structure-specific functions. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful method to quantitatively measure the structural diversity of OxPLs present in biological samples. This review outlines recent advances in analytical methods for OxPLs and their physiological relevance in health and diseases.

著者

Takanori Miyoshi Hiroo Miyashita Naomi Matsuo Miki Odawara Minako Hori Yoichi Hiraki Hirofumi Kawanaka

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1413-1418, 2021-10-01 (Released:2021-10-01)

参考文献数

20

被引用文献数

1

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The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1–3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0–24 h), delayed phase (24–120 h), and overall phase (0–120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

著者

Norio Ogata Hideaki Tagishi Motonori Tsuji

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.12, pp.1193-1200, 2020-12-01 (Released:2020-12-01)

参考文献数

41

被引用文献数

3

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Anisakiasis is common in countries where raw or incompletely cooked marine fish are consumed. Currently, effective therapeutic methods to treat anisakiasis are unavailable. A recent study found that wood creosote inactivates the movement of Anisakis species. Essential oil of Origanum compactum containing carvacrol and thymol, which are similar to the constituents of wood creosote, was reported to inactivate Anisakis by inhibiting its acetylcholinesterase. We examined whether wood creosote can also inhibit acetylcholinesterase. We examined the effect of components of wood creosote using the same experimental method. A computer simulation experiment (molecular docking) was also performed. Here, we demonstrate that wood creosote inactivated acetylcholinesterase in a dose-dependent manner with an IC50 of 0.25 mg/mL. Components of wood creosote were also tested individually: 5-methylguaiacol, p-cresol, guaiacol, o-cresol, 2,4-dimethylphenol, m-cresol, phenol and 4-methylguaiacol inactivated the enzyme with an IC50 of 14.0, 5.6, 17.0, 6.3, 3.9, 10.0, 15.2 and 27.2 mM, respectively. The mechanism of acetylcholinesterase inactivation was analyzed using a computer-based molecular docking simulation, which employed a three-dimensional structure of acetylcholinesterase and above phenolic compounds as docking ligands. The simulation indicated that the phenolic compounds bind to the active site of the enzyme, thereby competitively blocking entry of the substrate acetylcholine. These findings suggest that the mechanism for the inactivation of Anisakis movement by wood creosote is due to inhibition of acetylcholinesterase needed for motor neuron activity.

著者

Ryosuke Kori Keigo Murakami Yoshitake Nishiyama Tatsuya Toma Satoshi Yokoshima

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.3, pp.278-280, 2021-03-01 (Released:2021-03-01)

参考文献数

24

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We disclose our studies on a copper-mediated reaction of alkynes with trimethylsilyl azide to afford nitriles, and proposed a reaction mechanism, which involves an iodoalkyne and an iodotriazole as intermediates.

著者

Shinsuke Yamashita Shungo Imai Kenji Momo Hitoshi Kashiwagi Yuki Sato Mitsuru Sugawara Yoh Takekuma

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.8, pp.1151-1155, 2021-08-01 (Released:2021-08-01)

参考文献数

30

被引用文献数

1

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Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.

著者

Nahoko Uchiyama Junko Hosoe Naoki Sugimoto Kyoko Ishizuki Tatsuo Koide Mika Murabayashi Naoto Miyashita Kengo Kobayashi Yoshinori Fujimine Toshiyuki Yokose Katsuya Ofuji Hitoshi Shimizu Takashi Hasebe Yumi Asai Eri Ena Junko Kikuchi Kohei Kiyota Kazuhiro Fujita Yoshinobu Makino Naoko Yasobu Yoshiaki Iwamoto Toru Miura Koji Mizui Katsuo Asakura Takako Suematsu Hitomi Muto Ai Kohama Takashi Goto Masu Yasuda Tomohiko Ueda Yukihiro Goda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.7, pp.630-638, 2021-07-01 (Released:2021-07-01)

参考文献数

22

被引用文献数

4

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Recently, quantitative NMR (qNMR), especially 1H-qNMR, has been widely used to determine the absolute quantitative value of organic molecules. We previously reported an optimal and reproducible sample preparation method for 1H-qNMR. In the present study, we focused on a 31P-qNMR absolute determination method. An organophosphorus compound, cyclophosphamide hydrate (CP), listed in the Japanese Pharmacopeia 17th edition was selected as the target compound, and the 31P-qNMR and 1H-qNMR results were compared under three conditions with potassium dihydrogen phosphate (KH2PO4) or O-phosphorylethanolamine (PEA) as the reference standard for 31P-qNMR and sodium 4,4-dimethyl-4-silapentanesulfonate-d6 (DSS-d6) as the standard for 1H-qNMR. Condition 1: separate sample containing CP and KH2PO4 for 31P-qNMR or CP and DSS-d6 for 1H-qNMR. Condition 2: mixed sample containing CP, DSS-d6, and KH2PO4. Condition 3: mixed sample containing CP, DSS-d6, and PEA. As conditions 1 and 3 provided good results, validation studies at multiple laboratories were further conducted. The purities of CP determined under condition 1 by 1H-qNMR at 11 laboratories and 31P-qNMR at 10 laboratories were 99.76 ± 0.43 and 99.75 ± 0.53%, respectively, and those determined under condition 3 at five laboratories were 99.66 ± 0.08 and 99.61 ± 0.53%, respectively. These data suggested that the CP purities determined by 31P-qNMR are in good agreement with those determined by the established 1H-qNMR method. Since the 31P-qNMR signals are less complicated than the 1H-qNMR signals, 31P-qNMR would be useful for the absolute quantification of compounds that do not have a simple and separate 1H-qNMR signal, such as a singlet or doublet, although further investigation with other compounds is needed.

著者

Kenji Sugibayashi Mika Futaki Miyu Hashimoto Asuka Fukuhara Kengo Matsumoto Takeshi Oshizaka Shoko Itakura Hiroaki Todo

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.7, pp.639-645, 2021-07-01 (Released:2021-07-01)

参考文献数

28

被引用文献数

2

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The purpose of the present study was to evaluate whether iontophoresis (IP) accelerates the intradermal migration rate of medium molecular weight drugs. Sodium polystyrene sulfonate (PSA) and fluorescein isothiocyanate-dextran (FD) were used as model medium molecular weight acidic and non-electrolyte drugs, respectively. Low molecular weight acid and non-electrolyte drugs were also used for comparison. Drug-loaded excised split-layered skin (SL skin) was used in the experiment. SL skin was prepared using (i) whole skin was split once, (ii) the drug solution was applied on the lower skin, and (iii) the upper skin was layered onto the lower skin containing the drug solution as in the original skin. The effect of constant-current cathodal or anodal IP was applied to the SL skin, and the time course of the cumulative amount of drug migration from the SL skin through the dermis to the receiver was followed. In cases without IP and with anodal IP, the intradermal migration rates of medium molecular weight drugs were much lower than those of small molecules. The driving force for drug migration was thought to be simple diffusion through the skin layer. In contrast, cathodal IP significantly increased the intradermal migration rate of PSA not but of FD or low molecular weight drugs. This IP-facilitated migration of PSA was probably due to electrorepulsion. These results suggest that IP can be used to increase the intradermal migration of medium molecular weight charged drugs.

著者

Makoto Tsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.12, pp.1959-1968, 2019-12-01 (Released:2019-12-01)

参考文献数

132

被引用文献数

15 47

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Pain is a defense system that responds rapidly to harmful internal and external stimuli through the somatosensory neuronal pathway. However, damage to the nervous system through cancer, diabetes, infection, autoimmune disease, chemotherapy or trauma often leads to neuropathic pain, a debilitating chronic pain condition. Neuropathic pain is not simply a temporal continuum of acute nociceptive signals from the periphery, but rather due to pathologically altered functions in the nervous system, which shift the net neuronal excitatory balance toward excitation. Although alterations were long thought to be a result of changes in neurons, but an increasing body of evidence over the past decades indicates the necessity and sufficiency of microglia, the tissue-resident macrophages of the spinal cord and brain, for nerve injury-induced malfunction of the nervous system. In this review article, I describe our current understanding of the molecular and cellular mechanisms underlying the role of microglia in the pathogenesis of neuropathic pain and discuss the therapeutic potential of microglia from recent advances in the development of new drugs targeting microglia.

著者

Keita Yaginuma Shuichi Tanabe Hirokazu Sugiyama Manabu Kano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.6, pp.548-556, 2021-06-01 (Released:2021-06-01)

参考文献数

22

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Soft sensors play a crucial role as process analytical technology (PAT) tools. They are classified into physical models, statistical models, and their hybrid models. In general, statistical models are better estimators than physical models. In this study, two types of standard statistical models using process parameters (PPs) and near-infrared spectroscopy (NIRS) were investigated in terms of prediction accuracy and development cost. Locally weighted partial least squares regression (LW-PLSR), a type of nonlinear regression method, was utilized. Development cost was defined as the cost of goods required to construct an accurate model of commercial-scale equipment. Eleven granulation lots consisting of three laboratory-scale, two pilot-scale, and six commercial-scale lots were prepared. Three commercial-scale granulation lots were selected as a validation dataset, and the remaining eight granulation lots were utilized as calibration datasets. The results demonstrated that the PP-based and NIRS-based LW-PLSR models achieved high prediction accuracy without using the commercial-scale data in the calibration dataset. This practical case study clarified that the construction of accurate LW-PLSR models requires the calibration samples with the following two features: 1) located near the validation samples on the subspace spanned by principal components (PCs), and 2) having a wide range of variations in PC scores. In addition, it was confirmed that the reduction in cost and mass fraction of active pharmaceutical ingredient (API) made the PP-based models more cost-effective than the NIRS-based models. The present work supports to build accurate models efficiently and save the development cost of PAT.

著者

Tomoaki Ishida Kei Kawada Shumpei Morisawa Kohei Jobu Yasuyo Morita Mitsuhiko Miyamura

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.10, pp.1570-1576, 2020-10-01 (Released:2020-10-01)

参考文献数

24

被引用文献数

1 18

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Yokukansan is a Kampo formula that is commonly used by the elderly because it is expected to improve peripheral symptoms of dementia and delirium. However, side effects from its use are frequently reported in the elderly. In particular, pseudoaldosteronism caused by the licorice contained in yokukansan leads to hypertension, hypokalemia, and muscle weakness, which may result in death. This study aimed to identify the risk factors of pseudoaldosteronism with yokukansan use. Using cases reported in the Japanese Adverse Drug Report (JADER) database, the reporting odds ratio (ROR) was calculated and compared to assess the risk of pseudoaldosteronism for each licorice-containing Kampo formula. We also analyzed the risk factors for pseudoaldosteronism in patients taking yokukansan. Yokukansan (ROR 2.4, 95% confidence interval (CI) 1.9–2.8; p < 0.001) had a higher risk of pseudoaldosteronism than that of other licorice-containing Kampo formulas. Furthermore, the results of a logistic regression analysis in patients taking yokukansan showed that the licorice dose (OR 1.5, 95% CI 1.2–2.0; p < 0.01), older age (<70 years, OR 5.9, 95% CI 1.8–20; p < 0.01), dementia (OR 2.8, 95% CI 1.6–4.9; p < 0.001), low body weight (<50 kg, OR 2.2, 95% CI 1.1–3.5; p = 0.034) were risk factors for pseudoaldosteronism, Although not significant, treatment with loop diuretics (OR 1.8, 95% CI 0.98–3.5; p = 0.059) tended to increase the risk of pseudoaldosteronism. In summary, patients must understand the risk factors when considering taking yokukansan and reduce the licorice dose they consume.

著者

Ryuichiro Suzuki Yoshihiro Uesawa Yoshihito Okada Takumi Horikawa Yui Okabe Masaki Aburada Kunio Takahashi Kaoru Kinoshita

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.2, pp.199-202, 2021-02-01 (Released:2021-02-01)

参考文献数

11

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The 13C-NMR spectral data for the 15-carbon flavonoid skeleton in eleven methoxyflavones isolated from Kaempferia parviflora (Zingiberaceae) were processed by principal component analysis (PCA). Based on the PCA score plots, the methoxyflavones were categorized into three groups according to their structural features. The cytotoxicities of the methoxyflavones toward 3T3-L1 murine preadipocyte cells were evaluated by 3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and found to differ according to structure. The relationship between the 13C-NMR chemical shifts of the methoxyflavones and their cytotoxicities was investigated using Pearson’s correlation analysis. The 13C-NMR signal at C-10, a quaternary carbon, was correlated with cytotoxicity. Based on these results, a structural design which lowers the 13C-NMR chemical shift at C-10 would be important for the development of cytotoxic compounds. Although quantitative structure–activity and structure–property relationships are well established paradigms for predicting trends among a series of compounds, quantitative property–activity relationships have been relatively unstudied. This approach offers a new strategy for directing structure–activity relationship research.

著者

Nahoko Uchiyama Junko Hosoe Naoki Sugimoto Kyoko Ishizuki Tatsuo Koide Mika Murabayashi Naoto Miyashita Kengo Kobayashi Yoshinori Fujimine Toshiyuki Yokose Katsuya Ofuji Hitoshi Shimizu Takashi Hasebe Yumi Asai Eri Ena Junko Kikuchi Kohei Kiyota Kazuhiro Fujita Yoshinobu Makino Naoko Yasobu Yuko Yamada Yoshiaki Iwamoto Toru Miura Koji Mizui Katsuo Asakura Takako Suematsu Ai Kohama Yukihiro Goda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.1, pp.118-123, 2021-01-01 (Released:2021-01-01)

参考文献数

11

被引用文献数

8

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Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.

著者

Masayoshi Kumai Shungo Imai Shintaro Kato Ryo Koyanagi Kenkichi Tsuruga Takehiro Yamada Yoh Takekuma Mitsuru Sugawara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.4, pp.593-598, 2021-04-01 (Released:2021-04-01)

参考文献数

21

被引用文献数

4

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Nausea is a typical adverse event associated with opioids. In this study, we performed logistic regression analysis with the aim of clarifying the risk factors for nausea induced by extended-release oxycodone (ER-OXY). Furthermore, we constructed a decision tree (DT) model, a typical data mining method, to estimate the risk of oxycodone-induced nausea by combining multiple factors. A retrospective study was conducted on patients who newly received ER-OXY for cancer pain during hospitalization at Hokkaido University Hospital in Japan from April 2015 to March 2018. In logistic regression and DT analyses, the dependent variable was the presence or absence of nausea. Independent variables were the potential risk factors. First, univariate analyses were performed to screen potential factors associated with oxycodone-induced nausea. Then, multivariate and DT analyses were performed using factors with p-values <0.1 in the univariate analysis. Of 267 cases included in this study, nausea was observed in 30.3% (81/267). In multivariate logistic regression analysis, only female sex was extracted as an independent factor affecting nausea (odds ratio, 1.98). In the DT analysis, we additionally revealed that an age <50 years was a risk factor for nausea in female patients. Thus, our DT model indicated that the risk of ER-OXY-induced nausea was highest in the subgroup comprising females <50 years of age (66.7%) and lowest in male patients (25.1%). The DT model suggested that the factor of young women may be an increased risk of ER-OXY-induced nausea.

著者

Yuki Igarashi Miki Takahashi Tomoaki Tsutsumi Koichi Inoue Hiroshi Akiyama

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.3, pp.286-290, 2021-03-01 (Released:2021-03-01)

参考文献数

26

被引用文献数

6

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Monitoring analysis of 14 per- and polyfluoroalkyl substances (PFAS), 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B) and dodecafluoro-3H-4,8-dioxanonanoate (ADONA) in bottled drinking water, tea and juice samples was performed using LC coupled with tandem mass spectrometry (LC-MS/MS) and solid-phase extraction (SPE). In the electrospray negative ion mode, the limit of detection and limit of quantification (LOQ) values were 0.1 to 0.8 ng/mL and 0.2 to 1.6 ng/mL, respectively. The calibration curves were linear from LOQ to 50 ng/mL (r2 > 0.999). The SPE procedure (Presep PFC-II) was utilized for sample preparation and recovery rates for three standards (35, 70 and 140 ng/L) were 80.4–118.8% with relative standard deviation (RSD) ≤ 0.6%. Using the developed method, various samples (n = 54) from Japanese markets were investigated for PFAS and F-53B contamination, and values below the LOQ were observed. It is concluded that for monitoring products in the Japanese market, our method represents a significant improvement over complex techniques for the quantification of PFAS and related compounds from various foods.

著者

Maho Tsubota Kazuki Matsui Saaya Fukushi Kyoko Okazaki Fumiko Sekiguchi Atsufumi Kawabata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.3, pp.461-464, 2021-03-01 (Released:2021-03-01)

参考文献数

23

被引用文献数

6

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T-Type Ca2+ channels (T-channels), particularly Cav3.2, are now considered as therapeutic targets for treatment of intractable pain including visceral pain. Among existing medicines, bepridil, a multi-channel blocker, used for treatment of arrhythmia and angina, and pimozide, a dopamine D2 receptor antagonist, known as a typical antipsychotic, have potent T-channel blocking activity. We thus tested whether bepridil and pimozide could suppress visceral pain in mice. Colonic and bladder pain were induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and systemic administration of cyclophosphamide (CPA), respectively. Referred hyperalgesia was assessed by von Frey test, and colonic hypersensitivity to distension by a volume load with intracolonic water injection and spontaneous bladder pain were evaluated by observing nociceptive behaviors in conscious mice. The mice exhibited referred hyperalgesia and colonic hypersensitivity to distension on day 6 after TNBS treatment. Systemic administration of bepridil at 10–20 mg/kg or pimozide at 0.1–0.5 mg/kg strongly reduced the referred hyperalgesia on the TNBS-induced referred hyperalgesia and colonic hypersensitivity to distension. CPA treatment caused bladder pain-like nociceptive behavior and referred hyperalgesia, which were reversed by bepridil at 10–20 mg/kg or pimozide at 0.5–1 mg/kg. Our data thus suggest that bepridil and pimozide, existing medicines capable of blocking T-channels, are useful for treatment of colonic and bladder pain, and serve as seeds for the development of new medicines for visceral pain treatment.

著者

Nobuhiko Taguchi Minoru Yuriguchi Takuya Ando Ryosuke Kitai Hitomi Aoki Takahiro Kunisada

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.9, pp.1446-1449, 2019-09-01 (Released:2019-09-01)

参考文献数

16

被引用文献数

4 13

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During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.

著者

Yukihiko Aramaki Hidetoshi Arima Mamiko Takahashi Eriko Miyazaki Takatoshi Sakamoto Seishi Tsuchiya

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.10, pp.1461-1466, 2003 (Released:2003-10-01)

参考文献数

23

被引用文献数

4 5

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The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [32P]-labeled phosphodiester oligonucleotide ([32P]D-oligo, 18-mer) hybridizing to mouse interleukin 10 (IL-10) mRNA was used as a model D-oligo. In in vitro iontophoretic experiments, isolated hairless mouse skin was used with a horizontal diffusion cell. The enhancing effect of pulse depolarization (PDP) iontophoresis on the [32P]D-oligo permeation through the skin was better, and the skin irritation was less, than those of constant direct current (CDC) iontophoresis. The apparent fluxes of [32P]D-oligo were enhanced with the increasing current densities and [32P]D-oligo concentrations in the donor solution, whereas the enhanced flux decreased with the increasing NaCl concentrations in the donor solution. An optimum electric current was observed for the intradermal delivery of [32P]D-oligo, and intact [32P]D-oligo was detected within the skin after iontophoresis for 6 h. These results suggest that PDP iontophoresis may be useful for the intradermal delivery of antisense oligonucleotides.