YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
141 巻, 9 号
選択された号の論文の10件中1~10を表示しています
受賞総説
  • 三原 義広
    2021 年 141 巻 9 号 p. 1049-1055
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    For various pollutants with different specific gravity values, adsorbents having similar specific gravity values as those of target pollutants are necessary to achieve enough contact time. The purpose of this work is to introduce a self-vertical migration system to adsorbents for wastewater treatment. An alginate hydrogel composite with controlled specific gravity and buoyancy was successfully developed, which can first sink to the bottom of water and then float up on the surface after the adsorption. The alginate hydrogel composite was prepared using an alginate solution containing both glucose and yeast. In an experiment, the obtained beads first sank. However, 30 min later, most of them floated up to the water surface, where carbon dioxide was generated in the fermentation process. This behavior was repeated several times during the fermentation process, causing the beads to float. To confirm the efficiency of this unique property, the removal of cesium ions was demonstrated in a water column using Prussian Blue modified alginate gel beads with a repeated vertical migration system. The adsorbent showed a faster removal of cesium than the other adsorbents without the proposed system. We believe that the proposed system can be applied to treat large volumes of wastewater that cannot be stirred or pumped. Therefore, the novel adsorbent developed in this study is expected to significantly contribute to environmental remediation.

  • 吉田 一貴
    2021 年 141 巻 9 号 p. 1057-1061
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    Mast cells (MCs) are immune cells that are distributed in all tissues throughout the body, and their cytoplasm is rich in granules containing histamine and tryptase. When MCs recognize antigens through IgE bound to FcεRI, they release these mediators by degranulation. Because degranulation induces various type I allergic reactions, such as anaphylactic shock and hay fever, elucidation of the control mechanism of degranulation is important to the development of a therapeutic strategy for allergic diseases. It is known that the antigen-induced degranulation response is fine-tuned by various humoral factors via the activation of G protein-coupled receptors. We found that extracellular ATP enhanced antigen-dependent and -independent MC degranulation via activation of ionotropic P2X4 receptors. P2X4 receptor activation itself had no effect on MC degranulation, but significantly enhanced antigen-triggered degranulation. Stimulation of the P2X4 receptor potentiated the FcεRI-mediated tyrosine kinase signaling cascade. In addition to antigen-induced responses, P2X4 receptor signaling also affected antigen-independent MC responses. Thus, co-stimulation of ATP and Gi-coupled receptor agonists, such as prostaglandin E2 (PGE2) and adenosine, resulted in synergistic degranulation. The significance of P2X4 receptor signaling in allergic and inflammatory responses in vivo was confirmed by impaired responses of antigen-induced passive anaphylaxis and PGE2-induced increases in vascular permeability in P2rx4 knockout mice compared to that of wild-type mice. These results suggest that the P2X4 receptor is a potential therapeutic target for both antigen-dependent and -independent allergic reactions.

  • 東 顕二郎
    2021 年 141 巻 9 号 p. 1063-1069
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    70-90% of recently developed new drug candidates are poorly soluble in water, which creates a series of thorny challenges in developing its oral dosage forms, resulting in low bioavailability. In pre-formulation study, various specialized formulations have been developed to improve drug solubility. Intermolecular interactions between drug and excipients in the formulations can modify the drug state and achieve the improvement of drug solubility. Therefore, the understanding of intermolecular interaction is essential to design formulations with higher quality and to assure the quality as a pharmaceutical product. Solid-state NMR has attracted much attention as a promising method to evaluate the molecular state of a drug and the interaction between a drug and excipient in its formulation. I have applied solid-state NMR and its characteristic technique, namely magic-angle spinning (MAS), for various specialized formulations including amorphous solid dispersion, supersaturated solution, drug-loaded organic nanotube, and drug nanosuspension. The intermolecular interactions of drug and excipient in amorphous solid dispersion have been identified by 13C and 15N solid-state NMR. High-resolution MAS determined the interaction modes of drug and excipient in a supersaturated solution. The two-step dissolution profile of drug from organic nanotube was understood, based on the molecular states revealed by the combination of various solid-state NMR techniques. A suspended-state NMR clarified the nanostructure of drug nanoparticles dispersed in water. It is expected that more qualified pharmaceutical formulations with improved drug solubility can be designed based on the remarkable development of recent solid-state NMR technology.

  • 福田 達也
    2021 年 141 巻 9 号 p. 1071-1078
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    Increase in vascular permeability of the blood-brain barrier (BBB) is a distinct pathology following ischemic stroke. In previous studies, we demonstrated that liposomal drug delivery system (DDS)-based delivery of neuroprotectants is useful for treating cerebral ischemia/reperfusion injury. Additionally, our previous studies reported that combination therapy with liposomal fasudil plus tissue plasminogen activator (t-PA), a thrombolytic agent, brings about decrease in the risk of t-PA-derived cerebral hemorrhage and prolong the therapeutic time window of t-PA for treating acute ischemic stroke. However, accumulation of systemically administered liposomes into the brain parenchyma is still limited, and new technologies are needed that can overcome the BBB. The unique properties of leukocytes and exosomes, one of the extracellular vesicles, make them promising candidates for overcoming biological barriers (including the BBB) for drug delivery, as leukocytes and certain exosomes were reported to be able to permeate through the inflamed BBB in the ischemic stroke area. We prepared leukocyte-mimetic liposomes (LM-Lipo) via transfer of leukocyte membrane proteins by employing a phenomenon called intermembrane protein transfer, and demonstrated that LM-Lipo could pass through the layer of inflamed endothelial cells via regulation of intercellular junctions, like leukocytes. Additionally, we showed that LM-Lipo efficiently penetrated into spheroids of cancer cells, and inhibited their growth by entrapped doxorubicin. Taken together, it was suggested that imparting leukocyte-like characteristics to liposomes may be an effective approach to overcoming biological barriers. Herein, we summarize our findings regarding liposomal DDS for ischemic stroke therapy and recent approaches to develop biomembrane-mimetic DDS using leukocytes and exosomes.

  • 小出 裕之
    2021 年 141 巻 9 号 p. 1079-1086
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    Protein affinity reagents that specifically and strongly bind to target molecules are widely used in disease detection, diagnosis, and therapy. Although antibodies and their fragments are the gold standard in protein-protein inhibitors (PPIs), synthetic polymers such as linear polymers, dendrimers, and nanoparticles as cost-effective PPIs have attracted great attention as alternatives to antibodies. These polymers exhibit high affinity to the target by imitating natural protein-protein interactions. However, only a few in vivo applications have been reported. Here, our recent advances in the development of synthetic polymers for in vivo application are reviewed. Poly(N-isopropylacrylamide) (pNIPAm) was used as a model of synthetic affinity reagents. Incorporation of both sulfated carbohydrate and hydrophobic monomers into lightly crosslinked pNIPAm nanoparticles (NPs) captured and neutralized vascular endothelial growth factor (VEGF) and inhibited tumor growth upon intravenous injection into tumor-bearing mice. Modification of a liposome with the pNIPAm-based linear polymer increased the polymer circulation time after intravenous injection and improved the affinity for the target. The pNIPAm-based NPs delivered by oral administration captured the target small molecules and inhibited their absorption from the intestine. Our recent findings provide useful information for the design of synthetic polymers that capture target molecules in vivo.

  • 山越 博幸
    2021 年 141 巻 9 号 p. 1087-1094
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    Here, I describe a part of our efforts to develop synthetic strategies to construct bioactive natural products having a fused ring system. We have designed four chiral building blocks bearing contiguous quaternary stereocenters for the syntheses of bioactive C17-oxygenated steroids/triterpenoids and C9-oxygenated labdane diterpenoids. The compounds were stereoselectively synthesized from α-substituted glycolic acid (R)-3-methylcyclohex-2-enyl esters through Ireland-Claisen rearrangement to construct the stereocenters simultaneously. Synthetic utility of a β-type building block is highlighted by total syntheses of marrubiin (11 steps, 22%) and related seven labdane diterpene lactones, cyllenine C (12 steps, 29%), marrulactone (13 steps, 11%), marrulanic acid (14 steps, 10%), marrubasch F (12 steps, 14%), marrulibacetal (14 steps, 4%), marrulibacetal A (14 steps, 2%), and desertine (15 steps, 0.5%). These syntheses feature the construction of the [6.6.5]-tricyclic ring portion via a Pauson-Khand reaction, cleavage of the resultant cyclopentenone ring and an elongation of the C9 side chain by an epoxide opening reaction. The relative stereochemistry of desertine was determined to be 13R, 14S, 15S, 16R by some chemical conversions and NMR analysis. Further efforts toward total syntheses of oxygenated terpenoids using three other chiral building blocks and structure-activity relationship study of synthesized labdane diterpene lactones are currently underway in our laboratory and will be reported in due course.

一般論文
  • 柳 奈津代, 佐藤 宏樹, 澤田 康文
    2021 年 141 巻 9 号 p. 1095-1107
    発行日: 2021/09/01
    公開日: 2021/09/01
    [早期公開] 公開日: 2021/06/08
    ジャーナル フリー

    The difficulty and anxiety of nursery staff in administering medication to children at nursery schools has been reported, and its reduction is desired. However, the attitudes of mothers in requesting medication and the factors related to a high frequency of requests are not clear. We conducted an online survey of 600 mothers from April to May 2019 regarding the administration of medication at nursery school, and 301 mothers who had previously made such requests were analyzed. The results showed that 100.0% and 76.4% of the mothers felt gratitude and were apologetic for requesting medicine administration, respectively. In total, 47.5% of mothers expected pharmacists to support nursery staff in administering medication. Mothers' attitude of “I think the nursery staff should administer medication to my child more often” was significantly positively associated with a high frequency of the request in adjusted Model [adjusted odds ratio (AOR) 2.75, 95% confidence interval (CI) 1.36-5.55, p=0.005], while “I think the parents should manage so that the children do not have to take medicine in the nursery school so often” showed a negative association (AOR 0.33, 95% CI 0.17-0.66, p=0.002). Factors related to the involvement of community pharmacists were not significant. It is suggested that a change in mothers' attitudes could decrease the frequency of requests and consequently reduce the burden on nursery staff. Community pharmacists may support nursery staff to contribute to changing mothers' attitudes through medication consultations at the pharmacy.

  • 村橋 毅, 鈴木 彩夏, 本島 志穗, 樋口 敏幸
    2021 年 141 巻 9 号 p. 1109-1116
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    Occupational exposure of pharmacists to drugs during powder drug preparation in dispensing pharmacies was investigated. First, we determined frequently prescribed tipepidine hibenzate and ambroxol hydrochloride suspended in the air of the dispensing room. The median concentration of the drugs in the air was 0.01 μg/m3 and 0.02 μg/m3, respectively; these values indicate that the air in the dispensing room was contaminated with powder drug. To estimate drug exposure during powder drug preparation, drug dust was collected near the nose of workers. Analysis of the active ingredients of the drugs used in the preparation revealed that eight drugs, including bethanechol, l-carbocisteine, and zonisamide, were detected in the range of 1.5-1220 μg/m3. Assuming that the respiratory volume of an adult was 0.008 m3/min, it was estimated that 0.4-36 μg of the ingredients were exposed per prescription by multiplying concentration, respiratory volume and sampling time (3-5 min). Furthermore, the effect of wearing a medical mask on the drug powder exposure was evaluated using a self-made apparatus. When the amount of drug powder collected on filters that is either covered with or without a medical mask was compared, the covered filter exhibited reduced drug powder accumulation to less than 10% the amount collected on the uncovered filter. The present data suggested that a medical mask might decrease the drug dust allergies in dispensing pharmacists.

    Editor's pick

    Pharmacists are exposed to the drug when dispensing powder drug. The authors clarified the current status with scientific measurements. The pharmacists were exposed to 0.17 µg/d (median) of drug ingredients just in the dispensing room. Furthermore, dispensing drug powder increased the exposure to a maximum of 0.4–36 µg per one prescription. Although there are concerns about the health hazards of pharmacists due to exposure to drug dust, they found that wearing medical mask removed more than 90% of drug ingredient.

ケースレポート
  • 眞島 崇, 早坂 正孝, 大原 宏司
    2021 年 141 巻 9 号 p. 1117-1121
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    Various types of pre-learning—including pre-learning for practical training—provide pharmacy students with practical training and sufficient knowledge, skills, and attitudes for practical work. Opportunities in the medical field, including for pharmacists, have been greatly expanded for students with a hearing disability, and we have responded with appropriate training for such students. In this study, we report on the results of an evaluation of a survey on the preparatory training conducted by the students and the changes in their consciousness, such as in their level of understanding, knowledge, and self-confidence. Before the training, the participants' anxiety concerning items related to dispensing and communication were quite high; after the training, however, these anxiety levels were reduced. In addition, we were able to encourage the participant's concern for people and to face the difficulty of expressing words in letters, as well as to drive enthusiasm for the Objective Structured Clinical Examination (OSCE) and practical training. These results suggest that having a teacher as an assistant is useful for helping students with hearing disability in practical training.

  • 山﨑 陽子, 嶋田 昌彦
    2021 年 141 巻 9 号 p. 1123-1127
    発行日: 2021/09/01
    公開日: 2021/09/01
    ジャーナル フリー

    A 56-year-old woman visited an oral surgery clinic in October X with sudden pain in the left mandible. She was diagnosed with left mandibular osteomyelitis based on head computed tomography examination findings. The pain did not reduce even with amoxicillin and loxoprofen sodium hydrate. The patient was then referred to our clinic for treatment. Hainosankyuto (7.5 g/d), loxoprofen sodium hydrate (180 mg/d), and mecobalamin (1500 μg/d) alleviated the pain. However, numbness and tingling pain in the left part of the chin increased. Pregabalin 50 mg/d was then prescribed and then increased from 50 to 100 mg/d. The patient was diagnosed with antiresorptive agent-related osteonecrosis of the jaw (ARONJ). As the pain was exacerbated by discontinuation of the hainosankyuto, it was used continuously. The patient experienced no pain, even after discontinuing the mecobalamin and pregabalin. Platycodon root in hainosankyuto promotes drainage. The patient did not show any significant swelling because she took hainosankyuto during the early stages of inflammation. In addition, the pain resolved even when only hainosankyuto was used, possibly due to the analgesic effect of platycodon root, glycyrrhiza root, and peony root. Hainosankyuto may be an effective adjunctive treatment for patients with ARONJ whose pain is difficult to control with general treatment.

feedback
Top