Chemical & pharmaceutical bulletin最新文献_第4页

Concise and Highly Stereoselective Synthesis of β,β-Disubstituted α,β-Unsaturated Esters. 简洁、高立体选择性合成β，β-二取代α，β-不饱和酯。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00751

Minoru Ozeki, Mizuki Tsuda, Serina Yamanouchi, Momoe Yamakawa, Kanako Fukuda, Hirotaka Sasa, Takuya Matsumoto, Aya Niki, Maaya Nobata, Takashi Shigeta, Tetsuya Kajimoto, Kenji Arimitsu, Shinzo Hosoi, Hiroki Iwasaki, Naoto Kojima, Ikuo Kawasaki

引用次数: 0

Effects of Shape on the Disintegration Time and Friability of Sucroferric Oxyhydroxide-Containing Mini-Tablets. 形状对含氢氧化铁迷你片崩解时间及脆度的影响。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00675

Hiroaki Omori, Homare Kurashima, Nobuyuki Isshiki, Yasuharu Kashiwagura, Shinya Uchida

{"title":"Effects of Shape on the Disintegration Time and Friability of Sucroferric Oxyhydroxide-Containing Mini-Tablets.","authors":"Hiroaki Omori, Homare Kurashima, Nobuyuki Isshiki, Yasuharu Kashiwagura, Shinya Uchida","doi":"10.1248/cpb.c24-00675","DOIUrl":"https://doi.org/10.1248/cpb.c24-00675","url":null,"abstract":"Sucroferric oxyhydroxide is a phosphate binder for the treatment of hyperphosphatemia in patients with chronic kidney disease undergoing dialysis. This study aimed to determine the effects of tablet size, shape, and tensile strength on disintegration time and friability of sucroferric oxyhydroxide-containing mini-tablets. A linear relationship between the disintegration time and tensile strength was observed across all mini-tablets, except for those with smaller tablets (diameters: <1.8 mm). However, the relationship between friability and tensile strength was not significantly correlated under linear or exponential approximations. Explaining friability solely based on tensile strength was challenging, indicating the role of tablet shape. To visualize the effects of mini-tablet shapes and tensile strength on their disintegration time and friability, response aspects were analyzed. The response surface analysis revealed that the disintegration time was not affected by the tablet shape. The friability of the mini-tablets with a cup depth/diameter of 0.209 was lower (<0.2) than that of tablets with other cup depth/diameter across all tested ranges of tensile strength (1-6). A cup depth/diameter of 0.2 was identified as optimal for minimizing the friability of mini-tablets and can be implemented in commercial production without issues. In conclusion, tablet shape should be carefully considered during the development of mini-tablets to ensure low friability.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"257-263"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751401","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

Application of Isothermal Differential Scanning Calorimetry Equipped with a UV Probe for Photostability Assessment of Pharmaceutical Drugs in the Solid State. 紫外探针等温差示扫描量热法在固态药物光稳定性评价中的应用。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00323

Seiji Haruna, Eita Shimoda, Hiromasa Uchiyama, Kazunori Kadota, Hisashi Mimura, Yuichi Tozuka

{"title":"Application of Isothermal Differential Scanning Calorimetry Equipped with a UV Probe for Photostability Assessment of Pharmaceutical Drugs in the Solid State.","authors":"Seiji Haruna, Eita Shimoda, Hiromasa Uchiyama, Kazunori Kadota, Hisashi Mimura, Yuichi Tozuka","doi":"10.1248/cpb.c25-00323","DOIUrl":"https://doi.org/10.1248/cpb.c25-00323","url":null,"abstract":"Current methods for evaluating the photostability of pharmaceutical drugs typically separate the irradiation step from the analytical process, making it challenging to observe real-time photodegradation during irradiation. The use of HPLC equipped with UV and/or MS detectors, which are commonly used for quantitative analysis, requires considerable time to establish optimal conditions, and employs organic solvents, which are harmful to both the environment and the analyst. The aim of this study is to investigate the effectiveness of isothermal differential scanning calorimetry (DSC) equipped with a UV probe (photo-DSC) for evaluating the photostability of pharmaceutical drugs in the solid state. The response to light irradiation varies for different drugs, with some drugs exhibiting a thermal history showing endothermic behavior. To confirm the results of the endothermic reaction in photo-DSC, the percentage of the drug remaining after photo-irradiation was quantified using HPLC. Drugs that exhibited endothermic peaks consistently showed a decrease in residuals due to the photolysis reaction. In this study, we highlight the effectiveness of photo-DSC in evaluating the susceptibility of different drugs to photodegradation.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 8","pages":"745-751"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944223","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

Identification of Guanine-Quadruplex-Binding Peptides from the RGG3 Domain of TLS/FUS. TLS/FUS RGG3结构域鸟嘌呤四重结合肽的鉴定。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00413

Sayuri Takeo, Maiko Tabata, Hikari Okita, Natsuki Shibata, Kohei Sato, Nobuyuki Mase, Takanori Oyoshi, Tetsuo Narumi

{"title":"Identification of Guanine-Quadruplex-Binding Peptides from the RGG3 Domain of TLS/FUS.","authors":"Sayuri Takeo, Maiko Tabata, Hikari Okita, Natsuki Shibata, Kohei Sato, Nobuyuki Mase, Takanori Oyoshi, Tetsuo Narumi","doi":"10.1248/cpb.c25-00413","DOIUrl":"https://doi.org/10.1248/cpb.c25-00413","url":null,"abstract":"Guanine quadruplexes (G4s) are non-canonical nucleic acid structures that have emerged as attractive therapeutic targets owing to their involvement in diverse biological processes. Additionally, peptides derived from G4-binding proteins provide promising platforms for selective G4 recognition. In this study, we explored the G4-binding capacity of arginine-glycine-glycine (RGG)-rich sequences derived from the RGG3 domain translocated in liposarcoma/fused in sarcoma (TLS/FUS), a known G4 RNA binding protein. In this study, we synthesized a library of overlapping 15-mer peptides and evaluated their G4-binding affinities. Among the 10 evaluated native sequences, several peptides demonstrated measurable affinities toward G4 RNA structures, with STK5-1 exhibiting the highest G4-binding affinity. Furthermore, to investigate the impact of conformational constraints on G4 recognition, we introduced (E)-methylalkene dipeptide isosteres (MADIs) into selected Gly-Gly motifs, generating a series of RGG peptidomimetics. Subsequent binding assays revealed that some of these MADI peptidomimetics exhibited enhanced affinity and selectivity compared with their unmodified counterparts. Our findings offer new insights into the sequence and structural features governing G4-binding, establishing a foundation for the further development of peptide-based G4 ligands.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 10","pages":"938-943"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205811","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

Therapeutic Efficacy and Drug Metabolism of Griseorhodin A Induced by a Co-culture of Actinomycete Strain TMPU-20A002 and Mycobacterium smegmatis in Silkworm Infection Models. 放线菌TMPU-20A002与耻垢分枝杆菌共培养对家蚕感染模型的治疗效果及药物代谢

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00389

Akiho Yagi, Reo Sasaki, Ryuji Uchida

引用次数: 0

Effect of Particle Size of Powdered Cellulose Nanofibers as an Additive in the Production of Orally Disintegrating Mini-Tablets by Direct Powder Compression. 粉末纤维素纳米纤维粒径对直接粉末压缩生产口腔崩解小片的影响。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00042

Shohei Nakamura, Maya Shimasaki-Suzuki, Momoka Hamaoka, Ayumi Sakurada, Shinji Akiyama, Takatoshi Sakamoto

{"title":"Effect of Particle Size of Powdered Cellulose Nanofibers as an Additive in the Production of Orally Disintegrating Mini-Tablets by Direct Powder Compression.","authors":"Shohei Nakamura, Maya Shimasaki-Suzuki, Momoka Hamaoka, Ayumi Sakurada, Shinji Akiyama, Takatoshi Sakamoto","doi":"10.1248/cpb.c25-00042","DOIUrl":"https://doi.org/10.1248/cpb.c25-00042","url":null,"abstract":"Mini-tablets (MTs) allow for dosage adjustments according to children's weight and age. However, it is difficult to manufacture MTs with robust physical properties, and various formulation techniques are required. Adding cellulose nanofiber (CNF), a highly functional biomass material, to MTs improved the hardness and disintegration; however, the large variation in the weight and drug content of the resulting MTs remained a challenge. Therefore, this study analyzed the physical properties of CNF-containing MTs of different particle sizes and evaluated the effect of the particle size on MT manufacturing. CNF300, with an average particle size of approximately 300 µm, was pulverized to prepare CNF100, averaging 100 µm. The formulation included CNF (10, 30, and 50%), lactose hydrate, paracetamol, and magnesium stearate. The pharmaceutical powders mixed were loaded into a rotary tablet press equipped with a 3-mm multiple-tip tooling and compressed at 2, 5, and 8 kN forces. CNF100-containing MTs were manufactured via direct powder compression, and they showed lower variations in weight and drug content than those containing CNF300. The tensile strength of MTs containing CNF100 was smaller than that of those containing CNF300; however, a strength of ≥1 MPa (corresponding to ≥30 N hardness of a regular tablet) was obtained by setting the compression force to ≥5 kN. The MTs containing 30% CNF100 disintegrated in ≤30 s, regardless of the compression force. Thus, using smaller CNF particle sizes enabled the manufacturing of an orally disintegrating MT with adequate hardness and disintegration properties while also minimizing variations in MT weight and drug content.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 5","pages":"467-477"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118940","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

Structure-Signal Relationships of the δ-Opioid-Receptor (DOR)-Selective Agonist KNT-127-Part I: Impact of the Morphinan Skeleton on the G-Protein-Biased DOR Agonism. δ-阿片受体（DOR）选择性激动剂knt -127的结构-信号关系——第一部分：Morphinan骨架对g蛋白偏倚DOR激动作用的影响

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00012

Keita Kajino, Tomoya Sugai, Ryoji Kise, Riko Suzuki, Akihisa Tokuda, Yuki Sekiya, Tomoya Kakumoto, Risako Katamoto, Noriki Kutsumura, Yasuyuki Nagumo, Asuka Inoue, Tsuyoshi Saitoh

{"title":"Structure-Signal Relationships of the δ-Opioid-Receptor (DOR)-Selective Agonist KNT-127-Part I: Impact of the Morphinan Skeleton on the G-Protein-Biased DOR Agonism.","authors":"Keita Kajino, Tomoya Sugai, Ryoji Kise, Riko Suzuki, Akihisa Tokuda, Yuki Sekiya, Tomoya Kakumoto, Risako Katamoto, Noriki Kutsumura, Yasuyuki Nagumo, Asuka Inoue, Tsuyoshi Saitoh","doi":"10.1248/cpb.c25-00012","DOIUrl":"https://doi.org/10.1248/cpb.c25-00012","url":null,"abstract":"The δ-opioid receptor (DOR) is a promising target for developing novel analgesics due to its lower risk of causing side effects compared to the μ-opioid receptor (MOR), which is commonly associated with dependence, respiratory depression, and other adverse effects. KNT-127, a DOR-selective agonist with a morphinan skeleton, offers analgesic and antidepressant benefits without inducing convulsions at therapeutic doses, unlike the conventional DOR agonist SNC80. While previous studies have suggested that KNT-127 exhibits reduced β-arrestin recruitment, a signaling pathway implicated in adverse opioid effects, the ligand structural basis for this biased signaling remains unclear. In this study, we explored the structure-signal relationships of KNT-127, focusing on its quinoline moiety, which is known to serve as an address domain responsible for DOR selectivity. Modifying the quinoline moiety by removing the aromatic rings reduced DOR selectivity and potency in relation to G-protein activation while diminishing both the potency and efficacy of β-arrestin recruitment. These results suggest that the morphinan skeleton is critical for reduced β-arrestin recruitment, while the quinoline moiety differentially modulates G-protein activation and β-arrestin recruitment. Together, our study expands the message-address concept, previously limited to receptor selectivity, by providing structural insights into the G-protein-biased agonism of DOR agonists, thereby guiding the design of safer DOR-targeting therapeutics.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"246-256"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750362","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

Prediction of Intra-individual Variability in Bioequivalence Studies of 278 Formulations: Comprehensive Analysis Using Physicochemical and Pharmacokinetic Parameters. 278种制剂生物等效性研究的个体差异性预测：使用物理化学和药代动力学参数的综合分析。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00806

Masaki Higashino

{"title":"Prediction of Intra-individual Variability in Bioequivalence Studies of 278 Formulations: Comprehensive Analysis Using Physicochemical and Pharmacokinetic Parameters.","authors":"Masaki Higashino","doi":"10.1248/cpb.c24-00806","DOIUrl":"https://doi.org/10.1248/cpb.c24-00806","url":null,"abstract":"The purpose of the present study was to predict the intra-individual variability (%CVintra) values of Cmax using observed parameters of physicochemical and pharmacokinetic for a variety of formulations. A database was used to summarize the parameters of clinical bioequivalence (BE) studies of oral drugs, including the highest dose tablets, orally disintegrating tablets (ODT), and capsules (278 formulations [238 compounds]). As explanatory variables, %CVintra, inter-individual variability (%CVinter), absolute bioavailability (BA), Tmax, t1/2, dose number (Do), and dissolution rate (D%) were selected. Explanatory variables correlated with %CVintra were identified by multivariate analysis and grouped quantitatively by K-means clustering analysis. The %CVintra predictions compared three models of multiple regression, boosting tree, and neural network. In the neural network, the coefficient of determination (R2) and the root mean square error (RMSE) were the best, with good correlation between the predicted and observed values of the test data (R2 = 0.69). The explanatory variables used in this study are readily available from the literature of reference formulation and in vitro measurement. Therefore, predicting %CVintra for Cmax without conducting pilot studies is useful for clinical planning in the early stages of generic drug development. We believe that we could further contribute to speeding up and reducing the cost of generic drug development.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"349-354"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991658","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

New Nucleoside Derivatives for Hybridization-Assisted Catalysis of Site-Selective Acetylation of 2'-OH of RNA. 杂交辅助催化RNA 2'-OH位点选择性乙酰化的新核苷衍生物。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00068

Hayate Takasaki, Kentaro Kitazaki, Yurie Hadano, Hirotaka Murase, Jeongsu Lee, Yosuke Taniguchi, Shigeki Sasaki

引用次数: 0

Hyaluronan Tetrasaccharides Penetrate into the Skin by Passive Diffusion and Contribute to Skin Health. 透明质酸四糖通过被动扩散渗入皮肤，促进皮肤健康。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c23-00909

Yutaka Takagi, Madoka Kage

引用次数: 0