Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献_第5页

[Control of Heterogeneous Flow Reactions Using a Taylor Vortex Flow Reactor]. [利用Taylor涡流反应器控制非均相流动反应]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00122

Masahiro Hosoya

{"title":"[Control of Heterogeneous Flow Reactions Using a Taylor Vortex Flow Reactor].","authors":"Masahiro Hosoya","doi":"10.1248/yakushi.26-00122","DOIUrl":"https://doi.org/10.1248/yakushi.26-00122","url":null,"abstract":"To advance the manufacturing of drug substances under continuous flow conditions, homogeneous reaction systems are usually favored to enhance process control. However, heterogeneous reaction systems also need to be controlled in pharmaceutical production because drug substances are synthesized through multiple steps in various reaction systems. In this review, the author discusses a technological platform based on the Taylor vortex flow reactor which comprises a cylindrical tube and a rotating shaft, to streamline control of heterogeneous reaction systems. In the first example, the nucleation timing of reactive crystallization could be both accelerated and precisely controlled using a Taylor vortex flow reactor with high shear stress. This approach successfully mitigated adhesion to the reactor walls, thereby preventing clogging. In the second example, Taylor vortex flow reactors were applied to both liquid-liquid biphasic alkylation and continuous crystallization. Integration of these applications enabled achievement of overall continuous manufacturing in a single step. These examples confirm the high versatility and scalability of the Taylor vortex flow reactor for controlling heterogeneous reaction systems under continuous flow conditions.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 10","pages":"829-836"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Exposure to Environmental Chemicals and Children's Health: Findings from the Hokkaido Study]. [接触环境化学物质与儿童健康：来自北海道研究的发现]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00161-1

Yu Ait Bamai, Reiko Kishi

{"title":"[Exposure to Environmental Chemicals and Children's Health: Findings from the Hokkaido Study].","authors":"Yu Ait Bamai, Reiko Kishi","doi":"10.1248/yakushi.25-00161-1","DOIUrl":"10.1248/yakushi.25-00161-1","url":null,"abstract":"Rachel Carson's \"Silent Spring\" (1962) raised global awareness of the persistence of pesticides and their ecological impacts. Forty years later, the Hokkaido Study on Environment and Children's Health was initiated in 2002 as a large-scale, birth cohort study. Its primary aim is to investigate the health effects of environmental chemical exposure and to provide scientific evidence for environmental policy. Between 2002 and 2012, approximately 20,000 pregnant women from Hokkaido were recruited for the study. Their children, aged 13-23 years, were followed up. Maternal health and lifestyle data and blood samples were collected during the pregnancy. Medical records and umbilical cord blood samples were collected at the time of birth. Follow-up questionnaires were administered to children of various ages to collect information on child development, allergies, infections, and other health indicators. Face-to-face surveys conducted at school and during pubertal age selected a subset of participants living in the Sapporo area to collect detailed data, including cognitive and respiratory function tests, pubertal development evaluations, and biological sampling. Internal exposure to environmental chemicals was assessed using chemical analyses of blood and urine samples collected from mothers and children. This study provides important insights into the health effects of prenatal and postnatal chemical exposure. This presentation highlights the key findings of the Hokkaido Study, including exposure trends in the general Japanese population, associated health outcomes, and future research directions.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 4","pages":"277-284"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[MUC1 and SIGIRR as Negative Regulators of TLR Signaling: Expression, Function, and Anti-inflammatory Augmentation]. [MUC1和SIGIRR作为TLR信号的负调控因子：表达、功能和抗炎增强]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00162

Keiko Ueno-Shuto

{"title":"[MUC1 and SIGIRR as Negative Regulators of TLR Signaling: Expression, Function, and Anti-inflammatory Augmentation].","authors":"Keiko Ueno-Shuto","doi":"10.1248/yakushi.25-00162","DOIUrl":"10.1248/yakushi.25-00162","url":null,"abstract":"Toll-like receptors (TLRs) play a key role in initiating innate and acquired immunity, but their overactivation is also implicated in the development of autoimmune and chronic inflammatory conditions. To ensure tight regulation of TLR signaling, it is crucial to understand the expression and function of negative regulators of TLR signaling, such as mucin-1 (MUC1) and single immunoglobulin interleukin-1-related receptor (SIGIRR). Given these aspects, my research has revealed the following findings. 1) Membrane-tethered mucin glycoprotein MUC1 suppresses various TLR signaling pathways via its intracellular domain. 2) Lipopolysaccharide (LPS)-TLR4-p38 pathway suppresses SIGIRR gene expression. 3) Dominant-negative mutant of SIGIRR (Δ8-SIGIRR) reduces cell surface expression of wild-type SIGIRR in airway epithelial cells derived from cystic fibrosis (CF), characterized by chronic lung inflammation. The reduction of SIGIRR disrupts the SIGIRR/interleukin-18 receptor α (IL-18Rα) complex formation with interleukin-37 (IL-37), resulting in the impairment of the diverse anti-inflammatory activities of IL-37. 4) Enhancement of anti-inflammatory pathway via induction of SIGIRR/IL-18Rα expression and interaction. In CF cells, inhibition of histone deacetylase 3 (HDAC3) induces SIGIRR and IL-18Rα expression and restores IL-37-dependent anti-inflammatory responsiveness. To identify compounds as alternatives to IL-37, we developed a novel screening system capable of detecting SIGIRR/IL-18Rα heterodimer formation. Using this system, we discovered natural compounds that promote the interaction between SIGIRR and IL-18Rα. These findings provide fundamental insights into the treatment of inflammatory diseases and highlight the potential of MUC1 and SIGIRR as promising therapeutic targets.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 3","pages":"165-172"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Trends in Spontaneous Adverse Event Reports Following the Expansion of Pembrolizumab Indications in Japan]. 【在日本扩大派姆单抗适应症后自发性不良事件报告的趋势】。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00179

Kana Yamamoto, Ryoko Sakai, Manabu Akazawa

{"title":"[Trends in Spontaneous Adverse Event Reports Following the Expansion of Pembrolizumab Indications in Japan].","authors":"Kana Yamamoto, Ryoko Sakai, Manabu Akazawa","doi":"10.1248/yakushi.25-00179","DOIUrl":"10.1248/yakushi.25-00179","url":null,"abstract":"Pembrolizumab is an immune checkpoint inhibitor that has been widely used in cancer treatment, and its approved indications have expanded rapidly in recent years. However, the effects of this increase on immune-related adverse events (irAEs) remain unclear. Using data from the Japanese Adverse Drug Event Report (JADER) database and the National Database of Health Insurance Claims and Specific Health Checkups (NDB Open Data), we analyzed trends in the number and characteristics of spontaneously reported adverse events associated with pembrolizumab from fiscal years 2016 to 2024. The number of adverse event reports in JADER generally increased in parallel with prescription volume. Following the expansion of indications for gynecological cancers (such as breast, uterus, and cervix cancers) around 2021, a marked increase in reports was observed from 2022. During this period, the demographic profile of reported patients shifted from predominantly older males to middle-aged females. Regarding cancer types, the proportion of reports on breast and uterus cancers increased significantly, whereas those on lung cancer declined. In addition to pulmonary disorders, endocrine disorders became increasingly reported and represented the most frequent category in fiscal year 2022. The distribution of irAEs by cancer type suggested potential associations; pulmonary toxicity was more frequent in lung cancer, whereas endocrine toxicity was predominant in breast, uterus, and cervix cancers. Our findings indicate that the expansion of pembrolizumab indications has substantially altered the profile of reported immune-related adverse events in Japan, highlighting the need for ongoing pharmacovigilance tailored to cancer type and patient demographics.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 5","pages":"533-539"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Efficient Total Synthesis of Densely Functionalized Natural Products by New Complexity-Generating Strategy]. [通过新的复杂性生成策略高效全合成密集功能化天然产物]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00189

Koichi Hagiwara

引用次数: 0

[Development of Plant-derived Extracellular Vesicle-based Therapeutic Systems]. 植物源性细胞外囊泡治疗系统的发展

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00171-3

Makiya Nishikawa, Kosuke Kusamori, Shoko Itakura

{"title":"[Development of Plant-derived Extracellular Vesicle-based Therapeutic Systems].","authors":"Makiya Nishikawa, Kosuke Kusamori, Shoko Itakura","doi":"10.1248/yakushi.25-00171-3","DOIUrl":"10.1248/yakushi.25-00171-3","url":null,"abstract":"Plants have long supported human life as medicines and as sources of oxygen and food. Plant resources have played central roles in healthcare including traditional remedies and modern drugs such as aspirin. Recently, attention has shifted beyond small molecules to include higher-order biological structures such as extracellular vesicles (EVs). Plant-derived nanoparticles (pdNPs), obtained from edible plants by mechanical processing, are approximately 100 nm in size, biocompatible, and outperform mammalian EVs due to their safety, oral availability, stability, and low production cost. These features highlight the potential of pdNPs as platforms for drug delivery and therapeutic applications. Our group has focused on grains, legumes, and agro-industrial byproducts such as rice bran as sources of pdNPs. Corn-derived nanoparticles (cNPs) are abundant and enriched in carotenoids including lutein and zeaxanthin. We have demonstrated that cNPs could inhibit colon26 tumor cell growth by inducing G2 arrest and apoptosis, and also activate macrophages, suggesting dual antitumor and immunostimulatory effects. Furthermore, PEGylation improved pharmacokinetics, enhancing tumor accumulation, and therapeutic efficacy after intravenous administration. Rice bran-derived nanoparticles (rbNPs), prepared at high yield from low-value biomass, showed stronger tumor-specific growth inhibition than Doxil®, a clinically used liposomal formulation of doxorubicin, inducing apoptosis in colon26 cells and suppressing peritoneal dissemination in vivo. These findings highlight the potential of rbNPs as sustainable nanomedicines with therapeutic activity and environmental value. In conclusion, pdNPs, particularly cNPs and rbNPs, are cost-effective, safe, and sustainable biomaterials with great potential for advancing cancer therapy, vaccine development, and drug delivery systems.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 5","pages":"415-421"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Evaluating the Validity of the Action Limit and Predicted Environmental Concentration (PEC) in Environmental Risk Assessment Guidance for Novel Human Pharmaceuticals in Japan]. [评估日本新型人用药品环境风险评估指南中作用限值和预测环境浓度（PEC）的有效性]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00152

Shigechika Yamamoto, Taeko Maruyama-Komoda, Kenichi Masumura, Norihiro Kobayashi, Hiroshi Yamamoto, Takashi Yamada

{"title":"[Evaluating the Validity of the Action Limit and Predicted Environmental Concentration (PEC) in Environmental Risk Assessment Guidance for Novel Human Pharmaceuticals in Japan].","authors":"Shigechika Yamamoto, Taeko Maruyama-Komoda, Kenichi Masumura, Norihiro Kobayashi, Hiroshi Yamamoto, Takashi Yamada","doi":"10.1248/yakushi.25-00152","DOIUrl":"10.1248/yakushi.25-00152","url":null,"abstract":"As human pharmaceuticals are physiologically active substances, it is essential to assess their potential risk to ecosystems after being released into the environment. In Japan, the \"Guidance on the Environmental Risk Assessment in New Pharmaceutical Development\" (hereafter referred to as \"the guidance\") was issued in 2016. The guidance includes the environmental risk assessment (ERA) workflow, in which novel pharmaceuticals subjected to ecotoxicity testing are selected based on n-octanol/water partition coefficient (log Kow), action limit (0.01 µg/L), and predicted environmental concentration (PEC). However, for the ERA workflow, neither the action limit has been completely validated nor a method to calculate PEC has been sufficiently established. The objective of this study was to demonstrate the effectiveness and issues of the ERA workflow in the guidance. Using data accumulated from ecotoxicity studies and measured environmental concentration (MEC) data of human pharmaceuticals, we evaluated the validity of the action limit and PEC values. The action limit was found to be sufficiently on the safe side, and the PEC values (to median or 95th percentile MEC values) were generally on the safe side for the evaluated pharmaceuticals. Conversely, issues were also identified, which included a need to establish exemption rules for some specific pharmaceuticals with toxicological concerns at a concentration below the action limit and to refine the PEC calculation method based on the consideration of drug metabolism and environmental fate. The endeavor to address these issues will increase the reliability and effectiveness of the workflow.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 5","pages":"495-506"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Errata: GC-MS Analysis of Tris(1-aziridinyl)phosphine Oxide Flame Retardants in Textile Products]. [勘误：气相色谱-质谱分析纺织产品中氧化三（1-氮基）膦阻燃剂]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.146.265

Tomoko Ooshima, Tsuyoshi Kawakami

引用次数: 0

[Practical Pharmaceutical Researches Utilizing Clock Genes]. [利用时钟基因的实用药物研究]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00125

Kentaro Ushijima

{"title":"[Practical Pharmaceutical Researches Utilizing Clock Genes].","authors":"Kentaro Ushijima","doi":"10.1248/yakushi.25-00125","DOIUrl":"https://doi.org/10.1248/yakushi.25-00125","url":null,"abstract":"The biological clock system regulates gene transcription in approximately 24 h cycles, creating circadian rhythms with respect to drug pharmacokinetics and pharmacological efficacy. My research focuses on clinical applications of clock systems and the elucidation of pathophysiological mechanisms involving clock genes. In the present study, I aimed to identify the optimal timing of methylprednisolone (mPSL) administration to pediatric patients undergoing liver transplantation. A randomized clinical trial of 60 such patients demonstrated that evening administration (20:00) was associated with significantly fewer episodes of acute rejection and lower histological damage scores than morning administration (08:00). Notably, in patients who were not undergoing pretreatment with rituximab, mPSL administration in the evening completely prevented acute rejection within 14 d of transplantation. Pathophysiological studies revealed low clock gene expression rhythms in the adipose tissue of obese diabetic (ob/ob) mice, mediated through low histone H3K9 acetylation of the Dbp gene. Pharmacological correction of the abnormal histone acetylation increased the circulating adiponectin concentration and insulin sensitivity through peroxisome proliferator-activated receptor (PPAR)-γ mediated adipocyte differentiation. Importantly, low Dbp and PPAR-γ expression was also identified in human omental adipose tissue samples from patients with diabetes. I also discovered that diabetic microvascular complications can result from circadian clock dysfunction, with low zonula occludens-1 expression causing greater vascular permeability in the liver. Currently, I am evaluating the utility of microRNAs in extracellular vesicles as non-invasive biomarkers of intracellular clock gene expression. These findings should contribute to the optimization of chronotherapy and the identification of novel therapeutic targets.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 1","pages":"7-11"},"PeriodicalIF":0.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Programmed Medical Device (SaMD) and Orphan Drug Innovation Processes and Industrial Systems]. [程序化医疗设备（SaMD）和孤儿药创新过程和工业系统]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00140-3

Rei Goto, Shintaro Sengoku, Kota Kodama

{"title":"[Programmed Medical Device (SaMD) and Orphan Drug Innovation Processes and Industrial Systems].","authors":"Rei Goto, Shintaro Sengoku, Kota Kodama","doi":"10.1248/yakushi.25-00140-3","DOIUrl":"https://doi.org/10.1248/yakushi.25-00140-3","url":null,"abstract":"The innovation patterns and institutional environments of software as a medical device (SaMD) were empirically, comparatively, and institutionally analyzed as SaMD is attracting attention as innovative medical technology. Data were collected on SaMD products approved by the U.S. Food and Drug Administration (FDA) and medical providers (n=581 and 268, respectively). The relationships among SaMD use, the interaction of SaMD with existing medical devices, and company characteristics were structurally evaluated. The use of the current SaMDs as highly concentrated in the medical image processing field, with emerging information and communication technology companies producing many products. The relationship between SaMDs and hardware-type medical devices varied with their use purpose, based on which an innovation regime map for SaMDs was constructed. Next, the differences in reimbursement systems in Japan, the U.S., and Europe were comparatively analyzed, considering the policy implications for high-uncertainty technologies, such as SaMD and orphan drugs. We specifically focused on the cost-effectiveness-oriented reimbursement decision in Europe, the approval-for-reimbursement structure in Japan, and the range of individual decisions by payers in the United States. We summarized the actual state of price setting and payment models in each region (e.g., performance-based payments, price caps, and rebates). A framework for risk allocation between manufacturers and insurers is required when the value of medical technology is uncertain, suggesting a need for flexible and data-linked evaluations in future system designs.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 1","pages":"35-46"},"PeriodicalIF":0.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0