Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献

{"title":"[Development of Therapeutic Agents Targeting Higher-order Structures of Nucleic Acids in Neurodegenerative Diseases].","authors":"Norifumi Shioda","doi":"10.1248/yakushi.24-00209-2","DOIUrl":"https://doi.org/10.1248/yakushi.24-00209-2","url":null,"abstract":"<p><p>G-quadruplex (G4) is a unique nucleic acid structure that formed when a four-stranded structure is produced within a single-stranded guanine-rich sequence. Four guanine molecules form a square planar arrangement, termed G-quartet, which are stacked on top of each other to form the G4 structure in DNA (G4DNA) and in RNA (G4RNA). Recent studies have revealed that G4DNA and G4RNA are folded in cells, which suggested their biological and pharmacological significance in DNA replication, transcription, epigenetic modification, and RNA metabolism. In this review, I will provide an overview of G4, its identification methods, and the biological functions \"G4 biology\" that have been reported, as well as its relevance to the neurological diseases that we have reported. 1) we found a neuropathogenic mechanism, \"G4 prionoids\" in a CGG triplet repeat disease, Fragile X-associated tremor/ataxia syndrome (FXTAS). 2) G4 is a target of cognitive function therapy for ATR-X intellectual disability syndrome, in which mutations are found in a G4 binding protein ATRX. 3) 5-aminolevulinic acid is a potential candidate drug for treating some neurological diseases through the G4 binding ability.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 7","pages":"589-600"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555041","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}

{"title":"[Examination of Analytical Method for Polycyclic Aromatic Hydrocarbons in Creosote Products to Revise the Official Methods Based on \"Act on the Control of Household Products Containing Harmful Substances\"].","authors":"Iwaki Nishi, Taichi Yoshitomi, Masahiro Chiba, Hiroko Shioda, Mayumi Mimura, Toshiaki Yoshida, Soukichi Takagi, Hisayoshi Takai, Hiroshi Sakuragi, Hiroyuki Ohno, Maiko Tahara, Tsuyoshi Kawakami","doi":"10.1248/yakushi.25-00013","DOIUrl":"https://doi.org/10.1248/yakushi.25-00013","url":null,"abstract":"<p><p>Creosote, a derivative of coal tar, is used as a wood preservative. In Japan, regulations govern three specific polycyclic aromatic hydrocarbons (PAHs) present in creosote and creosote-treated wood: benzo[a]pyrene, benz[a]anthracene, and dibenz[a,h]anthracene. However, the existing standardized analytical methods in Japan have raised concerns regarding the safety of reagents employed and insufficient purification processes. To overcome these challenges, we developed an analytical method incorporating effective purification techniques, such as centrifugation, silica gel cartridges, and anion exchange cartridges, while eliminating the use of potentially carcinogenic dichloromethane. The validity of this method was evaluated through interlaboratory collaborative tests involving seven institutions. The analysis focused on 10 PAHs, including the three compounds regulated in Japan, across three concentration levels that encompassed current regulatory values. Validation results demonstrated that the method met the trueness and repeatability criteria, established at 70-120% and <10%, respectively. Most reproducibility data satisfied the <15% requirement. Exceptions were observed for two non-regulated compounds in Japan, as well as for samples with high matrix components spiked with the low concentrations of target analytes. The inherent difficulty of analyzing trace compounds in complex matrix components likely contributed to these unsatisfactory results. Despite these limitations, the developed method was validated as suitable for the analysis of at least three regulated PAHs in Japan.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 7","pages":"645-655"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555044","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}

{"title":"[Development of an NMR-Based Molecular Characterization Platform for Quality Assessment of Pharmaceutical Formulations].","authors":"Keisuke Ueda","doi":"10.1248/yakushi.25-00093","DOIUrl":"https://doi.org/10.1248/yakushi.25-00093","url":null,"abstract":"<p><p>Understanding the molecular-level properties of pharmaceutical formulations is essential for optimizing drug dissolution, stability, and delivery performance. In recent years, the structural complexity of formulations has increased significantly, incorporating multiple functional excipients. In this context, NMR spectroscopy has emerged as a powerful tool for evaluating the physicochemical behavior of active pharmaceutical ingredients (APIs) and excipients across diverse formulation platforms. NMR enables non-destructive, high-resolution analysis of molecular states under various physical conditions, including solids, solutions, and suspensions. Through techniques such as NMR relaxometry, pulsed-field gradient (PFG) NMR, and advanced pulse sequences, NMR provides insight into molecular mobility, miscibility, intermolecular interactions, and phase behavior. These molecular characteristics are closely related to key formulation attributes such as physical stability, dissolution performance, and bioavailability. This review outlines the principles and methodological advances in applying NMR to pharmaceutical formulation research, emphasizing its ability to quantify and differentiate complex coexisting states in situ. By offering direct access to critical molecular information, NMR serves as a diagnostic tool and a foundation for rational formulation design and quality control. As formulation strategies continue to evolve, the role of NMR in guiding the development and evaluation of innovative drug delivery systems is expected to become increasingly important.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 9","pages":"733-739"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971406","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}

{"title":"[An Intestinal Metabolite Exacerbates Stress-induced Diarrhea].","authors":"Narumi Ishihara, Shunsuke Kimura, Koji Hase","doi":"10.1248/yakushi.24-00190-2","DOIUrl":"https://doi.org/10.1248/yakushi.24-00190-2","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) constitutes a chronic functional gastrointestinal disorder characterized by abdominal pain and irregular bowel habits. Diagnosis typically hinges upon symptomatology, following the exclusion of organic pathologies such as intestinal inflammation and malignancies. IBS manifests with diverse symptoms attributable to aberrant intestinal function, including diarrhea, constipation, and bloating, stratified into four types based on the predominance of diarrhea versus constipation. Radical treatment for IBS remains elusive due to its unknown pathology and etiology, thereby necessitating symptom-focused therapeutic approaches. Certain conditions such as psychiatric disorders, intestinal inflammation, food sensitivities, and Small Intestinal Bacterial Overgrowth (SIBO) exhibit overlaps with or correlations to symptoms of IBS, suggesting that treatment targeting these conditions may ameliorate symptoms of IBS. Emotional stress emerges as a principal risk factor for IBS, precipitating alterations in stress hormone levels and intestinal motility, thereby instigating a spectrum of symptoms associated with the disorder. Additional risk factors for IBS exhibit considerable variability among individuals, encompassing dietary factors that stimulate or influence intestinal function, gluten, the presence of fermentable carbohydrates (fermentable oligosaccharides disaccharides monosaccharides and polyols: FODMAPs), and aspects of the intestinal microbiota and its metabolites. Notably, individuals with IBS demonstrate distinctive alterations in gut microbiota composition compared to healthy controls, indicative of dysbiosis. Furthermore, changes in metabolites such as short-chain fatty acids (SCFAs) in some IBS patients are recognized. In summary, while the precise etiology and underlying pathology of IBS remain elusive, management typically necessitates a multifaceted approach involving lifestyle modifications, targeted symptom therapies, occasional psychological support, and adjunctive measures to regulate the intestinal environment.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 8","pages":"667-672"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776310","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}

{"title":"[The Need for Phage Therapy in Combating Antimicrobial Resistance].","authors":"Kotaro Kiga","doi":"10.1248/yakushi.24-00190-4","DOIUrl":"https://doi.org/10.1248/yakushi.24-00190-4","url":null,"abstract":"<p><p>The escalating crisis of antimicrobial resistance poses a grave threat to global health and medicine in the 21st century. Phage therapy has emerged as a promising alternative to conventional antibiotics in addressing this urgent issue. Phages, unlike traditional antibiotics, leave the healthy microbiome largely undisturbed by selectively targeting and infecting their bacterial host. Additionally, phages can be readily genetically engineered to enhance their efficacy against specific bacterial strains. While some countries are slowly developing new regulations and implementing phage therapy in the clinic, widespread societal adoption remains limited. Phage therapy has the potential to revolutionize infection treatment; however, the unique biological properties of phages necessitate a multifaceted approach for the societal implementation of phage therapy. Recent research has focused on genetically engineering phages to enhance their capabilities or confer novel functions. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have facilitated the development of phages that target specific genes. Furthermore, the emergence of tRNA-carrying phages and phages that inhibit bacterial defense systems represents new classes of genetically engineered phages with enhanced bactericidal properties.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 8","pages":"679-688"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776316","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}

{"title":"[Development of Tumor-targeting Drug Delivery Systems Based on an Understanding of Polymer Characteristics and the Tumor-specific Environment].","authors":"Kenji Tsukigawa","doi":"10.1248/yakushi.24-00148","DOIUrl":"10.1248/yakushi.24-00148","url":null,"abstract":"<p><p>Tumor-specific active drug release from macromolecular antitumor drugs after tumor delivery is critical to achieve efficient cellular uptake of the active drug, thereby ensuring therapeutic efficacy. Upon reaching the tumor tissue, protease-facilitated depegylation of pegylated zinc protoporphyrin with ester bonds between PEG and ZnPP (esPEG-ZnPP) occurs, leading to a faster cellular uptake and superior antitumor efficacy compared to PEG-ZnPP with ether bonds (etPEG-ZnPP). This finding provides a viable strategy for achieving efficient tumor-specific drug release by utilizing an ester linkage between PEG and antitumor drugs. Another strategy involves using styrene-maleic acid copolymer (SMA), an amphiphilic polymer. Drug-encapsulating SMA aggregates disintegrate upon interaction with cell membrane components, releasing the encapsulated active drug. The author has demonstrated an improvement in the tumor accumulation of SMA-based macromolecular drugs by conjugating pirarubicin (THP), an anthracycline antitumor drug, with SMA. Furthermore, by conjugating various molecular weights of N-(2-hydroxypropyl)methacrylamide (HPMA) to THP via a hydrazone bond (P-THP, DP-THP, and SP-THP), the author has established a positive correlation between HPMA molecular weight and therapeutic efficacy as well as toxicity. Notably, P-THPs release THP under acidic conditions within tumor tissue; however, this release occurs solely outside tumor cells due to HPMA-mediated inhibition of cellular uptake. The author is currently developing macromolecular anticancer drugs using albumin for the tumor-targeted release of anticancer agents both intra- and extracellularly. The strategic development of tumor-targeting macromolecular antitumor drugs based on a comprehensive understanding of polymer characteristics and the tumor-specific environment is imperative for effective cancer therapy.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"85-92"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081158","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}

{"title":"[Establishment of Single-molecule Enzyme Activity Profiling (SEAP) Platform by Hybrid Technologies of Chemical Biology and Biophysics].","authors":"Toru Komatsu","doi":"10.1248/yakushi.24-00186-1","DOIUrl":"https://doi.org/10.1248/yakushi.24-00186-1","url":null,"abstract":"<p><p>In this study we have developed a method of profiling multiple \"single-molecules\" of enzymes in biological samples, by studying their activities as a form of single-molecule enzyme activity assay. The original method for single-molecule enzyme assay in microfabricated chamber devices was reported many years ago, but we for the first time report the application of this concept to identifying each enzyme in the chamber by simultaneously measuring activities against multiple substrates. Based on this idea, we developed the protein profiling technique to globally detect and \"count\" different sets of enzymes in biological samples containing various characterized and uncharacterized enzymes. We expect that the methodology will open up the application of single-molecule enzyme assay to discovering and using novel biomarker proteins.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 6","pages":"517-521"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200209","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}

{"title":"[Molecular Technologies to Utilize Light Energy for Chemical/pharmaceutical Research].","authors":"Naoyuki Toriumi","doi":"10.1248/yakushi.25-00009","DOIUrl":"https://doi.org/10.1248/yakushi.25-00009","url":null,"abstract":"<p><p>Organic molecules can absorb light energy to form excited states, from which various photophysical and photochemical processes such as heat, emission, and chemical reactions occur during deactivation to ground states. Therefore, it is highly important to control molecular properties in the excited states in many scientific fields including pharmaceutical sciences. Especially, the author has focused on the development of molecular technologies to utilize near-IR light, showing deep tissue penetration favorable for biomedical applications. The author has designed and synthesized 18π-electron tautomeric hydroxybenziphthalocyanines as functional near-IR-light-absorbing compounds with tunable aromaticity. Their near-IR absorption can be controlled by external stimuli such as chemical modifications and solvent effects. Additionally, the benziphthalocyanines were utilized for activatable near-IR photoacoustic imaging probes owing to their nonradiative thermal deactivation processes. The author also succeeded in developing a redox-switchable near-IR dye called benzitetraazaporphyrin. This molecule exhibits strong near-IR absorption in the 20π-electron antiaromatic reduced structure, while the 18π-electron oxidized structure is near-IR silent. The benzitetraazaporphyrin would be useful as near-IR probes working in reductive environments such as cancer cells.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 6","pages":"479-487"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200215","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}

{"title":"[Analytical Methods for Residual Compositional Substances of Agricultural Chemicals, Feed Additives, and Veterinary Drugs in Foods].","authors":"Takaaki Taguchi","doi":"10.1248/yakushi.24-00164-2","DOIUrl":"10.1248/yakushi.24-00164-2","url":null,"abstract":"<p><p>Pesticides, veterinary drugs, and feed additives (hereinafter referred to as \"pesticides\") can remain in foods when used in agricultural and livestock products. Since consuming a variety of foods every day can result in ingesting trace amounts of these pesticides, which may be harmful to health, risk management for residual pesticides in foods is necessary to prevent adverse effects. Based on the Food Sanitation Act, the Ministry of Health, Labour and Welfare (MHLW) has established maximum residue limits (MRLs) for each pesticide and each food type. Currently, approximately 770 pesticides have MRLs set. Since May 2006, Japan has implemented a positive list system, prohibiting the distribution of food containing residual pesticides exceeding the MRLs or uniform limit of 0.01 ppm for pesticides without established MRLs. Appropriate analytical methods are required to determine whether pesticides exceed the MRLs or uniform limit. Currently, MHLW has notified ten simultaneous analytical methods and approximately 350 individual analytical methods. However, many pesticides still lack developed analytical methods. These methods should be simple, quick, and accurate, but developing them is challenging. The National Institute of Health Sciences, in cooperation with local health institutes, registered conformity assessment bodies, and universities, is working on developing these analytical methods. This lecture introduces an overview and the challenges of analytical methods for detecting residual pesticides.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"101-104"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081217","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}

{"title":"[Legal Regulation and Analytical Method for Mycotoxin in Japan].","authors":"Tomoya Yoshinari","doi":"10.1248/yakushi.24-00164-5","DOIUrl":"10.1248/yakushi.24-00164-5","url":null,"abstract":"<p><p>Mycotoxins, toxic secondary metabolites produced by fungi, are present in food and feed worldwide. Acute and chronic dietary exposures can induce adverse health effects in humans and animals. Among the various mycotoxins, aflatoxins pose significant health concerns to the general public. In the early 1960s, a total of more than 100000 turkey poults died from an unknown turkey \"X\" disease in England. The disease was associated with Brazilian groundnut meal contaminated by Aspergillus flavus, from which aflatoxins were first isolated from the fungal culture broth. Subsequent studies revealed that aflatoxin B₁ (AFB₁) is the most potent carcinogen among all aflatoxins, affecting both humans and various animal species. The International Agency for Research on Cancer has classified AFB₁ as a Group 1 human carcinogen. Aflatoxins are present in a wide variety of food items, including cereals, nuts, fruits, and spices. A survey conducted in Japan between 2004 and 2006 revealed that peanut products, cacao products, peppers, and Job's tears were contaminated with aflatoxins. To reduce exposure, Japan has set a regulatory limit of 10 µg/kg for total aflatoxins [sum of AFB₁, aflatoxin B₂ (AFB₂), aflatoxin G₁ (AFG₁), and aflatoxin G₂ (AFG₂)] for all food items. The National Institute of Health Sciences has developed official analytical methods for determining aflatoxins in foods which are used for quarantine inspection of imported foods. In this symposium, the regulations and analytical methods for aflatoxins are introduced.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"117-120"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081252","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}