著者

山縣 友紀 五十嵐 芳暢 中津 則之 堀本 勝久 福井 一彦 植沢 芳広 山田 弘

出版者

一般社団法人 人工知能学会

雑誌

人工知能学会論文誌 (ISSN:13460714)

巻号頁・発行日

vol.34, no.2, pp.D-I81_1-18, 2019-03-01 (Released:2019-03-01)

参考文献数

40

被引用文献数

2

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In drug development, Drug-Induced Liver Injury (DILI) is a significant cause of discontinuation of development, and safety evaluation and management technology at early development stage are highly required. In recent years, toxicity prediction by in silico analysis is expected, and the machine learning research using omics data has attracted attention. However, the lack of explanation of machine learning is a problem. In order to make an appropriate safety assessment, it is necessary to clarify the mechanism of the toxicity (toxic course). In this study, we focus on the toxic course and propose an ontological model of the liver toxicity, which systematizes toxicity knowledge based on a consistent viewpoint. In application research, we introduce a prototype of a knowledge system for supporting toxicity mechanism interpretation. Based on the ontology, this system provides information flexibly according to the user's purpose by using semantic technologies. The system provides a graph visualization function in which nodes correspond to concepts and edges correspond to interactions between concepts. In such a visualization function, a toxic course map shows causal relationships of the toxic process. We illustrate examples of application to safety assessment and management by combining ontological and data-driven methodologies. Our ontological engineering solution contributes to converting from data to higher-order knowledge and making the data explainable in both human and computer understandable manner. We believe that our approach can be expected as a fundamental technology and will be useful for a wide range of applications in interdisciplinary areas.

著者

植沢 芳広

出版者

公益社団法人 日本化学会・情報化学部会

雑誌

日本化学会情報化学部会誌 (ISSN:09133747)

巻号頁・発行日

vol.36, no.3, pp.51, 2018 (Released:2018-12-24)

参考文献数

29

著者

植沢 芳広 内田 明宏 小山 茜 宇田川 三男 武田 直子 富澤 崇

出版者

一般社団法人日本医療薬学会

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.40, no.4, pp.215-221, 2014-04-10 (Released:2015-04-10)

参考文献数

7

被引用文献数

3 3

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Patients' waiting times in a community pharmacy closely correlate with prescription dispensing times. Therefore, to decrease patients' stress and present an index in dispensing operations, various factors affecting prescription dispensing were analyzed, and a time-prediction model was constructed. The time from when a prescription was accepted (ie, handed in by a patient) to its checking, as well as time-factors affecting dispensing and checking, were measured at Kitayurakucho Pharmacy. Additional aspects were taken into account, such as: acceptance time, whether questions needed to be asked of the prescribing physician, medicine-counting, number of pharmacists present, and number of patients in the waiting area. Thereafter, a statistical prediction model for waiting time was constructed. It was found that drug counting and congestion level significantly related to waiting time. A multivariate regression model with two such parameters indicated a highly accurate prediction level. It is expected that prediction of the waiting time with this model will be useful for alleviation of the patients' stress.

著者

永井 純子 植沢 芳広 加賀谷 肇

出版者

日本緩和医療学会

雑誌

Palliative Care Research (ISSN:18805302)

巻号頁・発行日

vol.10, no.1, pp.113-119, 2015 (Released:2015-02-03)

参考文献数

30

被引用文献数

1 4

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強オピオイドは,がん疼痛などの高度な痛みに適用される鎮痛薬である.強オピオイドを用いた疼痛緩和療法には多様な副作用が付随することから,適切な副作用管理を達成するための客観的根拠に基づくデータの解析が望まれる.そこで,本邦の副作用データベース(JADER)から,モルヒネ,フェンタニル,およびオキシコドンにおける副作用発現傾向を解析した.JADERから疼痛治療に用いた強オピオイドにより生じた副作用症例を抽出し,副作用の種類とその発現頻度を解析した.強オピオイドに共通する副作用の発現頻度は,薬物間で大きな相違が認められた.さらに,これらのオピオイドの副作用発現傾向を俯瞰する目的で主成分分析を行った結果,モルヒネはフェンタニルとオキシコドンの中間的な副作用の発現傾向を示すことが示された.以上の知見は,患者の副作用に応じた適切な薬剤選択による安全な薬物治療の確立に有用であると考えられる.

著者

植沢 芳広

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.4, pp.499-505, 2020-04-01 (Released:2020-04-01)

参考文献数

22

被引用文献数

4

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Toxicity testing is critical for new drug and chemical development process. A clinical study, experimental animal models, and in vitro study are performed to evaluate the safety of a new drug. The limitations of these methods include extensive time for toxicity testing, an ethical problem, and high costs of experimentation. Therefore computational methods are considered useful for estimating chemical toxicity. In silico toxicity prediction is one of the toxicity assessments that uses computational methods to predict and stimulate the toxicity of chemicals. In silico study aims to contribute to effective development of new drug and chemical design. In this study, quantitative structure-activity relationship (QSAR) models will be used to predict toxicities based on chemical structural parameters. Because toxicities are complicated physiological phenomena, a similar toxicity expression might cause a different pathway. Also, since many drugs with unknown mechanisms of actions are available, the application of artificial intelligence (AI)—which uses sophisticated algorithms— is increasingly used to predict toxicities. Recently, the QSAR model was applied to determine complex relations between chemical structures and toxicities. However, accuracy of QSAR for toxicity prediction remains an important issue. International competitions funded by public institutions can address this issue. Two important toxicity challenges were organized in the past decade; this article presents issues of toxicity based on these challenges.

著者

植沢 芳広

出版者

公益社団法人 日本薬剤学会

雑誌

薬剤学 (ISSN:03727629)

巻号頁・発行日

vol.77, no.5, pp.270-274, 2017-09-01 (Released:2017-09-01)

参考文献数

5

被引用文献数

1

著者

山縣 友紀 五十嵐 芳暢 中津 則之 堀本 勝久 福井 一彦 植沢 芳広 山田 弘

出版者

一般社団法人 人工知能学会

雑誌

JSAI大会論文集

巻号頁・発行日

vol.2018, pp.2F401, 2018

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<p>薬剤性肝障害は医薬品開発中止の主要因となっているが,肝毒性の発現機序(メカニズム)は複雑でありその全体像の把握は困難とされている.本研究では,オントロジー工学理論に基づき,機序の本質を捉えた肝毒性知識の体系化と記述枠組みのモデル化を行う.さらに,応用として創薬における安全性評価への適用について検討する.</p>

著者

永井 純子 植沢 芳広 加賀谷 肇

出版者

日本緩和医療学会

雑誌

Palliative Care Research (ISSN:18805302)

巻号頁・発行日

vol.10, no.3, pp.161-168, 2015 (Released:2015-08-12)

参考文献数

43

被引用文献数

2 6

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オキシコドンの薬効および体内動態は性差等の患者背景に依存することから,副作用と患者背景因子の関係の把握は臨床上重要な知見を与える可能性がある.そこで,独立行政法人医薬品医療機器総合機構・医薬品副作用データベース (JADER)を用いた解析を試みた.オキシコドン投与患者において,主要な副作用症例の年齢・性別による発現傾向の変化を観察した.オキシコドンに関連する重要な有害事象は,モルヒネおよびフェンタニルと共通して臨床的に認知されている譫妄,悪心・嘔吐等の症状であった.女性において悪心,下痢などの消化器症状が,男性においては間質性肺疾患が報告の多い有害事象であった.一方,非高齢者と比較して高齢者における有害事象は傾眠,譫妄等の報告が多かった.以上の結果は,オキシコドン投与時の副作用マネジメントの個別化において有用な知見となるものと期待される.

著者

植沢 芳広

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.2, pp.185-190, 2018-02-01 (Released:2018-02-01)

参考文献数

14

被引用文献数

4

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Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

著者

島田 智哉子 植沢 芳広 Ishii-Nozawa Reiko 石原 真理子 Kagaya Hajime 金本 大成 寺久保 繁美 中島 秀喜 高尾 浩一 杉田 義昭 坂上 宏

出版者

International Institute of Anticancer Research

雑誌

Anticancer Research (ISSN:2507005)

巻号頁・発行日

vol.34, no.10, pp.5405-5412, 2014-10

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Background: Fifteen 3-styrylchromones were subjected to quantitative structure?activity relationship (QSAR) analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to explore their biological activities. Materials and Methods: Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor-selectivity was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal human oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method followed by the density functional theory (DFT) method. Results: All 3-styrylchromone derivatives showed moderate-to-high tumor selectivity. Especially, compounds that have a methoxy group at 6-position of the chromone ring and hydroxyl group at 4'-position of phenyl group in styryl moiety [11] showed the highest tumor-selectivity. On the other hand, their cytotoxicity against normal cells showed good correlation to the descriptors that reflect hydrophobic interaction and molecular shapes. Conclusion: Multivariate statistics with chemical descriptors for the location of substituted group, molecular shape and electrostatic interaction may be useful for designing the most favorable compound with higher tumor selectivity.

著者

安田 一貴 田中 伸明 富澤 崇 水田 尚子 植沢 芳広 鈴木 正

出版者

日本医療薬学会

雑誌

日本医療薬学会年会講演要旨集

巻号頁・発行日

vol.21, 2011-09-09

著者

植沢 芳広

出版者

公益社団法人 日本化学会・情報化学部会

雑誌

日本化学会情報化学部会誌

巻号頁・発行日

vol.26, no.4, pp.114-114, 2008

著者

植沢 芳広

出版者

公益社団法人 日本化学会・情報化学部会

雑誌

日本化学会情報化学部会誌 (ISSN:09133747)

巻号頁・発行日

vol.26, no.4, pp.114-114, 2008 (Released:2008-12-30)

参考文献数

11