Chemical & pharmaceutical bulletin最新文献_第7页

Developing Methods for the Synthesis of Ligand-Oligonucleotide Conjugates for Drug Discovery Applications. 用于药物发现应用的配体-寡核苷酸缀合物的合成方法的发展。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00387

Takashi Osawa

引用次数: 0

Insights on Molecular Interaction between Polymer and Poorly Water-Soluble Loratadine in Solid Dispersion from Molecular Dynamics and Experiments. 聚合物与难水溶性氯雷他定在固体分散中分子相互作用的分子动力学和实验研究。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00326

Jincao Tang, Huai He, Chi Ma, Anqi Luo, Yu Zhou, Qin Xiao, Zheng Lu, Tianbing Guan, Shuangkou Chen, Taigang Zhou, Huimin Sun, Aiping Wang, Haijun Huang, Chuanyun Dai

{"title":"Insights on Molecular Interaction between Polymer and Poorly Water-Soluble Loratadine in Solid Dispersion from Molecular Dynamics and Experiments.","authors":"Jincao Tang, Huai He, Chi Ma, Anqi Luo, Yu Zhou, Qin Xiao, Zheng Lu, Tianbing Guan, Shuangkou Chen, Taigang Zhou, Huimin Sun, Aiping Wang, Haijun Huang, Chuanyun Dai","doi":"10.1248/cpb.c25-00326","DOIUrl":"https://doi.org/10.1248/cpb.c25-00326","url":null,"abstract":"This study aims to employ molecular dynamics (MD) methods to predict the miscibility and molecular interactions between loratadine (LOR) and polymers, thereby designing drug formulations with enhanced water solubility. The research seeks to improve formulation design efficiency and accelerate the drug development process. A viable approach to enhance the solubility of poorly soluble drugs involves creating solid dispersions (SDs) with hydrophilic polymers. However, the specific intermolecular interactions within this system warrant further investigation. In this study, MD simulations were conducted to assess the molecular miscibility and interactions between LOR and 4 polymers. Then, the simulation results were verified by physical experiments. The findings demonstrate that LOR exhibits substantial miscibility with these polymers. Among the 2 drug loading ratios, S4 and S7 exhibited the strongest interactions, respectively. The solubility experiment also confirmed this result. It is confirmed that MD can be used to predict the formation of SDs, and this method can also predict the water solubility of the system, underscoring the utility of MD in advancing the development of SDs.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 8","pages":"713-723"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944378","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

Bicarbonate Buffer Dissolution Test Using the Floating Lid Method: Inter-Laboratory Reproducibility of pH Maintenance. 浮盖法碳酸氢盐缓冲液溶解试验：pH维持的实验室间重现性。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00283

Masahiro Fushimi, Masaki Higashino, Shotaro Ikuta, Hiroyuki Yoshida, Kiyohiko Sugano

{"title":"Bicarbonate Buffer Dissolution Test Using the Floating Lid Method: Inter-Laboratory Reproducibility of pH Maintenance.","authors":"Masahiro Fushimi, Masaki Higashino, Shotaro Ikuta, Hiroyuki Yoshida, Kiyohiko Sugano","doi":"10.1248/cpb.c25-00283","DOIUrl":"https://doi.org/10.1248/cpb.c25-00283","url":null,"abstract":"Bicarbonate buffer (BCB) has been difficult to use in conventional dissolution tests because its pH rapidly increases as CO2 escapes from the air-water interface. Recently, the floating lid method was introduced as a convenient method for using BCB in dissolution tests. This study aimed to confirm the inter-laboratory reproducibility of pH maintenance of BCB using the floating lid method for both paddle and flow-through cell (FTC) methods. Three pharmaceutical companies and 1 academic research institute participated in this study. A BCB solution (pH 6.5, 15 mM) was employed as the test solution. In the paddle method, the pH values of BCB rapidly increased without the floating lid. The pH change (ΔpH) at 6 h ranged from +1.66 to +1.82 (50 rpm) and +1.96 to +2.02 (100 rpm). The floating lid effectively maintained the pH values in all laboratories, with ΔpH ranging from +0.13 to +0.17 (50 rpm) and +0.21 to +0.25 (100 rpm). The standard deviation of ΔpH was within 0.05 at both 50 and 100 rpm. Similarly, in the FTC method, without the floating lid, ΔpH ranged from +1.71 to +1.77 (reservoir), +1.59 to +1.72 (FTC), and +1.73 to +1.76 (sampling tube). With the floating lid, ΔpH ranged from +0.05 to +0.10 (reservoir), +0.05 to +0.09 (FTC), and +0.26 to +0.39 (sampling tube). The standard deviation of ΔpH was within 0.05. In conclusion, the inter-laboratory reproducibility of pH maintenance of BCB using the floating lid method was confirmed for both the paddle and FTC methods.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 8","pages":"692-697"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820684","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

Diastereoselective Synthesis of Pyrroloindolines by Palladium-Dihydroxyterphenylphosphine-Catalyzed C3-Dearomative Arylation/Cyclization of Substituted Tryptamines. 钯-二羟基terphenylphospine催化取代色胺的c3 -去芳基化/环化非对映选择性合成吡咯啉。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00404

Miyuki Yamaguchi, Haruna Jimbo, Hideyuki Konishi, Mitsuru Kondo, Kei Manabe

引用次数: 0

Development of Biological-Event Manipulators Triggered by Light-Activated Compounds. 光激活化合物触发生物事件操纵器的研制。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00503

Naoya Ieda

{"title":"Development of Biological-Event Manipulators Triggered by Light-Activated Compounds.","authors":"Naoya Ieda","doi":"10.1248/cpb.c25-00503","DOIUrl":"https://doi.org/10.1248/cpb.c25-00503","url":null,"abstract":"Photoresponsive molecular tools have become powerful platforms for manipulating biological functions with high spatiotemporal precision. In this review, we highlight recent advances in the development of light-activated compounds that interact with key signaling molecules and microenvironments. Inspired by various chemical reactions triggered by light-matter interactions, this review covers three representative systems: photoactivatable peroxynitrite (ONOO-) generators, visible-light-driven nitric oxide (NO) releasers, and optochemical oxygen (O2) scavengers. ONOO-, a reactive nitrogen species formed from NO and superoxide (O2-), plays a critical role in protein nitration and cellular oxidative stress. By designing molecules that generate both NO and O2- upon light exposure, efficient ONOO- release was achieved and used to induce nitration reactions. For NO manipulation, the authors developed a class of photoresponsive releasers that utilize photoinduced electron transfer (PeT) to enable blue-to-red light-triggered NO release. These photoresponsive releasers allowed optical control of vasodilation both ex vivo and in vivo, which forms the basis of a minimally invasive approach to modulate blood flow. In addition, a light-responsive O2 scavenger was developed to induce localized hypoxia in cell cultures. The light-responsive O2 scavenger enabled optical regulation of the hypoxia-responsive pathway and activation of the transient receptor potential ankyrin 1 (TRPA1) calcium channel, which underscores the utility of this approach. Together, these studies illustrate how rational molecular design, combined with precise photochemical control, can create innovative systems for probing and directing biological events. These technologies are valuable as both a basic research tool and for potential future therapeutic applications.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 10","pages":"919-926"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205723","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

¹H-NMR Spectroscopy Study of the Formation of Inclusion Complexes between Cucurbit[7]uril and Ciprofloxacin, Levofloxacin, and Lomefloxacin. 瓜bbbbil与环丙沙星、左氧氟沙星、洛美沙星包合物形成的1H-NMR研究。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00362

Rie Nakashima, Mai Inadomi, Hiroyuki Tsutsumi, Tomonori Ohata, Hirohito Ikeda

{"title":"1H-NMR Spectroscopy Study of the Formation of Inclusion Complexes between Cucurbit[7]uril and Ciprofloxacin, Levofloxacin, and Lomefloxacin.","authors":"Rie Nakashima, Mai Inadomi, Hiroyuki Tsutsumi, Tomonori Ohata, Hirohito Ikeda","doi":"10.1248/cpb.c25-00362","DOIUrl":"https://doi.org/10.1248/cpb.c25-00362","url":null,"abstract":"Owing to the recent detection of pharmaceutical residues in aquatic environments, the development of methods for their removal has attracted increasing research attention. Considering the rich host-guest chemistry of cucurbit[7]uril (CB[7]), which can form stable inclusion complexes with various compounds, we envisioned that CB[7] could be used for capturing pharmaceutical residues in aquatic environments. In this study, using 1H-NMR spectroscopy, we examined the formation of inclusion complexes between CB[7] and new quinolone antibiotics that have been linked to the emergence of resistant bacteria, that is, ciprofloxacin hydrochloride monohydrate (CPFX), levofloxacin hydrochloride (LVFX), lomefloxacin hydrochloride (LFLX), and pazufloxacin mesylate (PZFX). The results showed that CPFX, LVFX, and LFLX formed inclusion complexes with CB[7] at a molar ratio of 1 : 1, with complex formation constants (K) of 0.529, 0.877, and 3.65 (×104 M-1), respectively, whereas PZFX did not. This difference was attributed to the presence or absence of a piperazine ring, indicating that it is a critical feature for the formation of inclusion complexes with CB[7]. In addition, the thermodynamic parameters calculated using van't Hoff plots revealed that LVFX and LFLX with a methyl group on the piperazine ring expel high-energy water from the cavity of CB[7] more efficiently, resulting in larger K values. Because the piperazine ring structure is commonly found in many drugs, CB[7] can be expected to capture other drugs apart from those evaluated in this study. Therefore, CB[7] is a promising candidate as a host molecule for use in drug removal in aquatic environments through host-guest chemistry.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 10","pages":"968-973"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250007","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

Benzomalvin G and H, an Atropisomeric Pair of Dimethoxylated Quinazolinobenzodiazepine Alkaloids Produced by Aspergillus fumigatiaffinis. 烟熏曲霉产生的二甲氧基喹唑啉苯二氮卓类生物碱的atrosom异构对G和H。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00430

Shinji Kishimoto, Rikuto Takahashi, Kenji Watanabe

引用次数: 0

Efficient Drug Release from Liposomes Introduced Tetrazine Derivatives with Pyrimidine Rings Using Click Chemistry. 利用Click化学方法引入了具有嘧啶环的四嗪衍生物脂质体的高效药物释放。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00591

Mizuho Yamasaki, Masayuki Munekane, Kento Kannaka, Kohei Sano, Toshihide Yamasaki, Takahiro Mukai

{"title":"Efficient Drug Release from Liposomes Introduced Tetrazine Derivatives with Pyrimidine Rings Using Click Chemistry.","authors":"Mizuho Yamasaki, Masayuki Munekane, Kento Kannaka, Kohei Sano, Toshihide Yamasaki, Takahiro Mukai","doi":"10.1248/cpb.c24-00591","DOIUrl":"10.1248/cpb.c24-00591","url":null,"abstract":"We developed a novel drug release method using a bioorthogonal inverse electron demand Diels-Alder reaction on liposomal membranes. Based on reports that replacing pyridine with pyrimidine in tetrazine derivatives improves the reaction rate with strained dienophiles, we investigated if liposomes with tetrazine derivatives containing pyrimidine rings efficiently release drugs via click chemistry. We synthesized and evaluated a tetrazine compound (Tz2) bearing a pyrimidine ring. The reaction rate constant of Tz2 with a norbornene (NB) derivative, 5-norbornenecarboxylic acid (NBCOOH), was higher than that of Tz1 with a pyridine ring. Liposomes containing the synthesized Tz2 (Tz2-liposomes) were prepared, and the reaction between Tz2 and NBCOOH on the liposomal membranes was confirmed using high-resolution mass spectrometry. We encapsulated indium-111-labeled diethylenetriaminepentaacetic acid ([111In]In-DTPA) in liposomes as a model drug. The release of [111In]In-DTPA from Tz2-liposomes was observed after the addition of NBCOOH, with release dependent on NBCOOH concentration. Moreover, release from Tz2-liposomes was significantly higher than that from Tz1-liposomes. These results suggested that tetrazine derivatives with pyrimidine rings efficiently released drugs, likely due to enhanced reaction rates. These findings would advance the development of controlled drug release methods using click chemistry.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"108-111"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490975","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

Effect of Alcohols on the Skin Permeation of Various Drugs. 酒精对各种药物皮肤渗透的影响。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00716

Yuki Ofuchi, Haruna Setoyama, Tsubasa Miyoshi, Kumi Kawano, Yoshiyuki Hattori, Yasuko Obata

{"title":"Effect of Alcohols on the Skin Permeation of Various Drugs.","authors":"Yuki Ofuchi, Haruna Setoyama, Tsubasa Miyoshi, Kumi Kawano, Yoshiyuki Hattori, Yasuko Obata","doi":"10.1248/cpb.c24-00716","DOIUrl":"10.1248/cpb.c24-00716","url":null,"abstract":"In this study we have focused on three types of alcohols: ethanol (EtOH), 2-propanol (IPA), and 1-propanol (NPA), and examined the skin permeability of drugs with different physicochemical properties: ketoprofen (KPF; hydrophobic), cimetidine (CMT; slightly hydrophobic), and caffeine (CF; hydrophilic). The results revealed EtOH particularly enhanced the skin permeation of CF, while IPA enhanced skin permeation regardless of the type of drug. In contrast, NPA significantly increased the skin permeability of KPF and CMT, but had little effect on CF. The differing effects of the alcohols on skin permeation appear to be linked to the physicochemical properties of the drugs. KPF is more hydrophobic than the other drugs, suggesting that it uses the intercellular pathway in the stratum corneum for permeation. CMT has intermediate properties between hydrophilic and hydrophobic, resulting in low skin permeability and ineffective utilization of both the transepidermal and transappendageal pathways. CF mainly utilized the transappendageal pathways for skin permeation because of its smaller molecular weight and more hydrophilic as compared with the other drugs. These results suggest that the effect of different alcohols on enhancing drug skin permeation is not uniform and that the optimal alcohol for enhancing permeability may vary depending on the drug. Therefore, the selection of appropriate additives based on the physicochemical properties of the drug, such as hydrophilicity, hydrophobicity, and molecular weight, is crucial for developing effective transdermal formulation.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"291-297"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771442","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

Evaluation of Time-Dependent Deformation Behavior of Pharmaceutical Excipients in the Tableting Process. 药用赋形剂在片剂过程中随时间变化的变形行为的评价。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00710

Daisuke Mizunaga, Satoru Watano

{"title":"Evaluation of Time-Dependent Deformation Behavior of Pharmaceutical Excipients in the Tableting Process.","authors":"Daisuke Mizunaga, Satoru Watano","doi":"10.1248/cpb.c24-00710","DOIUrl":"https://doi.org/10.1248/cpb.c24-00710","url":null,"abstract":"Tableting is a critical process in the manufacture of pharmaceutical tablets that directly influences product quality. Ensuring consistent quality between the research and development phase and commercial-scale production is essential during scale-up. In this study, we investigated methods for evaluating time-dependent deformation behavior using four excipients that exhibit different compression deformation behaviors. Dicalcium phosphate dihydrate (DCPD) shows no viscoelasticity, whereas lactose monohydrate (LAC), cornstarch (CS), and microcrystalline cellulose (MCC) exhibit viscoelasticity and viscoplasticity, although the degree of viscosity varies between them. In addition to investigating the known strain rate sensitivity (SRS), we performed mechanical energy evaluation based on the area under the force-displacement curve and stress relaxation tests. A trapezoid waveform was applied during the test, with loading punch speeds of 0.5 and 100 mm/s, and a dwell time of 4.5 s. The SRS value for DCPD approached approximately one, indicating no speed dependence, and the SRS increased in the order of LAC < MCC < CS, consistent with previous studies that used a saw-tooth waveform. Among the mechanical energies, the ratio of plastic flow energy to plastic energy, which depends on dwell time, followed a similar trend to SRS for the three materials other than DCPD. We conclude that axial stress relaxation is affected by machine deformation, whereas radial stress relaxation provides insight into the viscous behavior of the material. Under the test conditions, the effects of the punch-displacement profile and compression pressure on the mechanical energy and stress relaxation were more pronounced than those of SRS.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"213-226"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699676","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