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

Microplastics are small pieces of plastic that are less than 5 mm in length. These plastics have been detected in various environments, including the ocean, soil, and air. Their abundance have raised concerns regarding their potential effects on living organisms, including humans. The surface of microplastics degrades due to external factors such as ultraviolet rays and water waves in the environment. Therefore, assessing the biological impact of microplastics and considering their state of degradation is important. Among the physical properties of microplastics, we focused on the chemical degradation of microplastics. Specifically, we used vacuum ultraviolet (VUV) light to accelerate the degradation of polyethylene (PE) and prepared PE samples representing the degradation of PE to varying degrees. The surface properties of PE samples prepared using VUV were similar to those obtained from the environment. Cytotoxicity tests were then used to evaluate the effects of undegraded and degraded PE on cells. We found that the severity of cytotoxicity increased with the extent to which the PE would have been degraded, suggesting that the degree of degradation is strongly linked to the severity of the observed deleterious effects on living organisms. In conclusion, this finding contributes to our understanding of the effects of polyethylene microplastics on the human body.

The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However, discrepancies in the information on drug interaction are reported between J-PI and foreign databases. This study aimed to evaluate various information sources on N/r drug interactions. We categorized and compared information on N/r drug interactions from the J-PI, prescribing information from foreign regulatory agencies, guidance from the National Institutes of Health and University Health Network, the Ontario coronavirus disease 2019 (COVID-19) Science Advisory Table, University of Liverpool, Lexicomp, and the Japanese Society of Pharmaceutical Health Care and Sciences (JSPHCS). We assessed information quantity, missing data in J-PI, predicted change of the area under the blood concentration-time curve (AUC) for nirmatrelvir or co-administered drugs, and the information source consistency. From these information sources, we compiled a dataset with 115 contraindications and 203 precautions for N/r co-administration, and 51 contraindications are missing in J-PI. Among them, at least 12 drugs have large predicted AUC changes with N/r (AUC ≥5-fold or <1/5 of the baseline value). Nine of these 12 drugs are included as contraindications in Lexicomp and the JSPHCS. The consistency among the information sources is low. Information in the J-PI alone may be insufficient and Lexicomp or the JSPHCS guidelines should be useful because of their large amounts of information and wide coverage of drugs with large AUC changes. Due to low source consistency, multiple sources are needed for clinical management.

In Japan, only few hospitals have pharmacists in their secondary emergency rooms to record medication history and provide drug information in real time. In this study, we investigated the benefits of pharmacist intervention in secondary emergency rooms by comparing the time taken by the pharmacists and non-pharmacists in the emergency room to record the medication history in the electronic medical record and the accuracy of its content. The study period was from September 1 to September 30, 2022, and included patients who were transported to our hospital for emergency care between 9:00 and 16:30. We compared the time taken between the patient's arrival until the recording of their medication history and the accuracy of the record by the emergency room pharmacists and non-pharmacists (paramedics or medical clerks). The study included 58 patients whose medication histories were collected by pharmacists, and 11 patients whose histories were collected by non-pharmacists. For pharmacists, the median time to record medication history in the electronic medical record was 12 min, whereas for non-pharmacists, it was 19 min, which was significantly different (p=0.015). The pharmacists accurately recorded the medication history of 98.3% (57/58) of patients, whereas non-pharmacists accurately recorded it for only 54.5% (6/11) of patients, with a significant difference (p<0.01). We observed that in secondary emergency rooms, when pharmacists were responsible for recording the patients' medication histories, it resulted in rapid and accurate sharing of medication history.

Boron neutron capture therapy (BNCT) is expected to be a promising next-generation cancer treatment. In 2020, Japan, which has led the research on this treatment modality, was the first country in the world to approve BNCT. The boron agents that have been clinically applied in BNCT include a caged boron compound (mercaptoundecahydrododecaborate: BSH) and a boron-containing amino acid (p-boronophenylalanine: BPA). In particular, the BPA preparation Steboronine^® is the only approved drug for BNCT. However, the problem with BPA is that it is poorly retained in the tumor and has very low solubility in water. This cannot be overlooked for BNCT, which requires large amounts of boron in the tumor. The high dosage volume, together with low tumor retention, leads to reduced therapeutic efficacy and increased physical burden on the patient. In the case of BSH, its insufficient penetration into the tumor is problematic. Based on drug delivery system (DDS) technology, we have developed a next-generation boron pharmaceutical superior to Steboronine^®. Our approach involves the redevelopment of BPA using innovative ionic liquid formulation technology. Here, we describe previous boron agents and introduce our recent efforts in the development of boron compounds.

Burow's solution is a 13% aluminum acetate solution used for treating chronic suppurative otitis media. However, multiple formulations for Burow's and neo-Burow's solutions are used as in-hospital preparations. Each formulation uses different types and amounts of reagents, and takes a different time to prepare. Thus, the ions, including aluminum ion (Al³⁺), and other molecules in the prepared Burow's and neo-Burow's solutions are not identical, and the pH also differs. Furthermore, details about the antibacterial activity of these preparations are unknown. This study evaluated the stability and antibacterial activity of four Burow's and two neo-Burow's solutions prepared using different methods. Preparation times ranged from 20 min to 3 d, and the pH ranged from 2.2 to 4, meaning some solutions were more acidic or more basic than the pH 3 devised by Burow. In addition, the Al³⁺ concentrations ranged from 0.05 to 1.51 mol/L, meaning some solutions were more concentrated or diluted than 13% aluminum acetate (0.64 mol/L). One of the Burow's solutions we prepared produced a white residue after 14 d, making it difficult to ensure stability. In addition, confirming the antibacterial activity of another Burow's solution against the test bacteria was problematic. Despite the differences in pH and Al³⁺ concentrations between the various Burow's and neo-Burow's solutions, the antibacterial activity was equivalent. It was considered necessary to use the basic data obtained in this study to select a formulation for each hospital. Evaluation of the antibacterial activity of each formulation in clinical settings will be a subject for future study.

Since around 2021, products claiming to contain a Δ⁹-tetrahydrocannabinol (THC) analog with different lengths of alkyl chain at C-3 position have been sold on the internet in Japan. Δ⁹-THC has a pentyl group derived from the precursor olivetol at the C-3 position. These products include liquid cartridges for electronic cigarettes, herbal products, and gummy products. This study analyzed and determined the ingredients in five oil products distributed on the internet from 2022 to 2023 that claim to contain THC analogs. Samples of each product were used for GC-MS and LC-MS measurements. After isolating and purifying the unknown components from the products, structural analysis was performed by measuring ¹H, ¹³C-NMR and various two-dimensional NMR [HH correlation spectroscopy (H-H COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple-bond correlation (HMBC), and nuclear Overhauser effect spectroscopy (NOESY)]. The analysis identified Δ⁸-tetrahydrocannabivarin (THCV), Δ⁹-THCV, Δ⁸-tetrahydrocannabutol (THCB), Δ⁹-THCB, Δ⁸-tetrahydrocannabihexol (THCH), Δ⁹-THCH, Δ⁸-3-octyl-THC (THCjd) and Δ⁹-THCjd. These compounds were Δ⁸-THC or Δ⁹-THC analogs with different lengths of alkyl chain at C-3 position. Meanwhile, Δ⁴⁽⁸⁾-iso-THCV and Δ¹¹-THCB were identified as minor components of the product, and were considered to be the reaction byproducts of the synthesis of the Δ⁸-THC or Δ⁹-THC analogs. In the future, there are concerns about the distribution of products containing new THC analogs. Therefore, continuous provision monitoring of newly detected in the products is important.

Sulfur- or nitrogen-containing compounds from medicinal plants exhibit various biological activities such as anticancer potential. Developing efficient strategies to isolate or synthesize these compounds or their derivatives is a remarkable achievement. We have isolated several sulfur-containing compounds such as tetrahydro-2H-difuro[3,2-b:2',3'-c]furan-5(5aH)-one derivatives from Allium plants. We have devised a unique approach for the rapid preparation of thiopyranones using the regioselective sequential double Diels-Alder reaction; we used a naturally-occurring chemically-unstable intermediate such as thioacrolein, which is produced from allicin, a major component in garlic. The cytotoxicity of the synthetic thiopyranones against cancer stem cells (CSCs) was equal to or higher than that of (Z)-ajoene, the reference compound.