著者

袴塚 高志

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.10, pp.978-982, 2014 (Released:2016-09-30)

参考文献数

7

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2011年1月のアンチスタックスに引き続き,2014年4月にプレフェミンが一般用医薬品として製造販売の承認を受けた.前者は赤ブドウ(Vitis venefera L.)の葉,後者はチェストツリー(Vitex agnus-castus L.)の果実に由来する西洋ハーブ医薬品である.アンチスタックスは軽度の静脈還流障害による諸症状の改善,特に足のむくみを改善する内服薬として既に販売されており,プレフェミンが月経前症候群を緩和する内服薬として流通する日も遠くないものと思われる.ドラッグストア等の店頭で健康食品として販売されている西洋ハーブの中には,欧州で一般用医薬品として扱われているものもあり,医薬品としての規制を受けずに流通することに関して,かねてより安全性や品質保証の面で問題視されてきた.医薬品の承認はあくまでも個別の案件であり,西洋ハーブ全般が一般用医薬品に移行するという話ではないが,海外の生薬製剤を我が国の一般用医薬品として承認申請する道筋が明示され,実際の承認例も出てきたことは,天然物医薬品に係る薬事行政ならびに産業振興の上で画期的な出来事と言える.本稿では,医薬品,食品および健康食品の関連性について触れつつ,西洋ハーブ医薬品という新しいカテゴリーが誕生するまでの経緯を概説したい.

著者

田中 理恵 河村 麻衣子 水谷 佐久美 袴塚 高志 花尻(木倉) 瑠理

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.142, no.6, pp.675-681, 2022-06-01 (Released:2022-06-01)

参考文献数

9

被引用文献数

2

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Arylcyclohexylamines are a category of substances to which the anesthetic ketamine belongs. The arylcyclohexylamines have been reported to act as antagonists of the N-methyl-d-aspartate (NMDA) receptor. An analog of ketamine, 2-(ethylamino)-2-(3-methoxyphenyl)-cyclohexanone (methoxetamine; MXE), has been controlled as a narcotic in Japan and overdoses of MXE have been reported to cause health problems. In recent years, MXE derivatives have beendetected in illegal products in Japan. In this study, we describe the identification of three MXE derivatives, 2-(3-methoxyphenyl)-2-(propylamino)cyclohexan-1-one (methoxpropamine; MXPr), 2-(isopropylamino)-2-(3-methoxyphenyl)cyclohexan-1-one (methoxisopropamine; MXiPr) and 2-(3-methoxyphenyl)-2-(propylamino)cyclohexan-1-one (deoxymethoxetamine; DMXE), from illegal products.

著者

内山 奈穂子 鎌倉 浩之 政田 さやか 辻本 恭 細江 潤子 徳本 廣子 丸山 卓郎 合田 幸広 袴塚 高志

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

pp.17-00136, (Released:2017-07-19)

参考文献数

14

被引用文献数

2

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In January 2017, counterfeits of the hepatitis C drug 'HARVONI® Combination Tablets' (HARVONI®) were found at a pharmacy chain through unlicensed suppliers in Japan. A total of five lots of counterfeit HARVONI® (samples 1-5) bottles were found, and the ingredients of the bottles were all in tablet form. Among them, two differently shaped tablets were present in two of the bottles (categorized as samples 2A, 2B, 4A, and 4B). We analyzed the total of seven samples by high-resolution LC-MS, GC-MS and NMR. In samples 2A, 3 and 4B, sofosbuvir, the active component of another hepatitis C drug, SOVARDI® Tablets 400 mg (SOVARDI®), was detected. In sample 4A, sofosbuvir and ledipasvir, the active components of HARVONI®, were found. A direct comparison of the four samples and genuine products showed that three samples (2A, 3, 4B) are apparently SOVARDI® and that sample 2A is HARVONI®. In samples 1 and 5, several vitamins but none of the active compounds usually found in HARVONI® (i.e., sofosbuvir and ledipasvir) were detected. Our additional investigation indicates that these two samples are likely to be a commercial vitamin supplement distributed in Japan. Sample 2B, looked entirely different from HARVONI® and contained several herbal constitutents (such as ephedrine and glycyrrhizin) that are used in Japanese Kampo formulations. A further analysis indicated that sample 2B is likely to be a Kampo extract tablet of Shoseiryuto which is distributed in Japan. Considering this case, it is important to be vigilant to prevent a recurrence of distribution of counterfeit drugs.

著者

田中 理恵 河村 麻衣子 袴塚 高志 花尻(木倉) 瑠理

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.11, pp.1405-1413, 2020-11-01 (Released:2020-11-01)

参考文献数

15

被引用文献数

8

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Lysergic acid diethylamide (LSD) is a hallucinogen, synthesized from ergot alkaloid, and controlled as a narcotic in Japan. Recently, LSD derivatives have appeared as designer drugs, all over the world. In previous study, we reported identification and analysis of four LSD derivatives in four paper sheet products. In this study, we detected three additional LSD derivatives from three paper sheet products, which were obtained from September 2019 to March 2020 in Japan. We extracted the compounds from paper sheet products with methanol for LC-MS, high-resolution MS and GC-MS analyses. The compounds were identified as 4-cyclopropionyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1cP-LSD), N-methyl-N-isopropyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo-[4,3-fg]quinoline-9-carboxamide (MIPLA), 4-butyryl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1B-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. As well as other N1-acylated LSD derivatives, 1cP-LSD and 1B-LSD were easily deacylated to LSD during GC-MS analysis, we have to be careful to analyze these compounds.

著者

田中 理恵 河村 麻衣子 袴塚 高志 花尻(木倉) 瑠理

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.5, pp.739-750, 2020-05-01 (Released:2020-05-01)

参考文献数

21

被引用文献数

8

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To prevent the abuse of new psychoactive substances (NPS), a total of 2372 substances and two plants are controlled as “Designated Substances” in Japan as of September 2019. Although the distribution of these substances has decreased for the past three years, newly-emerged NPS are still being found. In this study, we detected four lysergic acid diethylamide (LSD) derivatives as designer drugs from four paper sheet products, which were obtained from 2014 to 2017 in Japan. The compounds were identified as 4-Acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52), N,N,7-triethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ETH-LAD), 7-Allyl-N,N-diethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (AL-LAD), N,N-diethyl-7-methyl-4-propionyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1P-LSD), by GC-MS, LC-MS, LC-Q-TOF-MS and NMR analyses. Further, we studied the extraction methods of LSD derivatives from paper sheet, and the analytical conditions of GC-MS, LC-MS and LC-FL(fluorescence). Among LSD derivatives, 1P-LSD have been controlled as designated substances (Shitei Yakubutsu) under the Pharmaceutical and Medical Device Act in Japan since April 2016. For the legislation of the other derivatives identified in this study, the evaluation of their pharmacological properties are now in progress.

著者

柴田 寛子 野村 祐介 河上 強志 山本 栄一 安藤 大介 内山 奈穂子 徳本 廣子 小出 達夫 迫田 秀行 吉田 寛幸 阿部 康弘 袴塚 高志 五十嵐 良明 蓜島 由二 石井 明子 伊豆津 健一 本間 正充 合田 幸広

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.142, no.8, pp.867-874, 2022-08-01 (Released:2022-08-01)

参考文献数

5

被引用文献数

1

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Particular batches of Moderna mRNA Coronavirus Disease 2019 (COVID-19) vaccine were recalled after foreign particles were found in some vaccine vials at the vaccination site in Japan in August 2021. We investigated the foreign particles at the request of the Ministry of Health, Labour and Welfare. Energy dispersive X-ray spectroscopy analysis suggested that the foreign particles found in the vials recalled from the vaccination sites were from stainless steel SUS 316L, which was in line with the findings of the root cause investigation by the manufacturer. The sizes of the observed particles ranged from <50 μm to 548 μm in the major axis. Similar foreign particles were also detected in 2 of the 5 vaccine vials of the same lot stored by the manufacturer, indicating that the foreign particles have already been administered to some people via vaccine. Observation of the vials of the same lot by digital microscope found smaller particles those were not detected by visual inspection, suggesting that more vials were affected. Contrarily, visual inspection and subvisible particulate matter test indicated no foreign particles in the vials of normal lots. Possible root cause and strategies to prevent such a deviation were discussed from technical and regulatory aspects.

著者

袴塚 高志

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.6, pp.783-788, 2020-06-01 (Released:2020-06-01)

参考文献数

6

被引用文献数

1

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The latest edition of the Japanese Pharmacopoeia (JP) is the second supplement to the 17th edition containing 324 herbal medicines, of which 176 are crude drugs and 35 are Kampo extracts. Although 148 prescription Kampo extracts are covered by national health insurance, only 35 are listed in the latest JP. However, the sales volume of these 35 Kampo extracts accounts for more than 70% of the total sales volume of Kampo products, as Kampo formulas with higher sales volumes are preferentially listed in the JP. The JP officially defines the origin and description of the listed crude drugs and Kampo extracts and elaborates on their limited values and testing methods. As crude drugs and Kampo extracts are derived from natural products and have the characteristics of traditional medicines, some degree of variation has been experienced during their long-term use, which is one of the crucial differences from chemical drugs. The Japanese Pharmacopoeia Committee on Crude Drugs promotes standardization of the JP by reflecting the actual Japanese market situation. This review explains the characteristics of natural and traditional medicines in crude drug-related items, the JP drafting process and points to be noted, and the significance of listing in the JP.

著者

渥美 さやか 大沼 美貴 末永 恵美 丸山 卓郎 菱田 敦之 木内 文之 小林 進 合田 幸広 袴塚 高志

出版者

日本食品化学学会

雑誌

日本食品化学学会誌 (ISSN:13412094)

巻号頁・発行日

vol.20, no.3, pp.178-189, 2013

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ブラックコホシュはキンポウゲ科サラシナショウマ属Cimicifuga racemosaの根及び根茎に由来する西洋ハーブであるが、健康食品等として流通するブラックコホシュ製品からはC. racemosa以外の近縁種の混入が報告されており、基原鑑別法の確立が望まれてきた。そこで我々は、葉緑体trnL領域のDNA配列を基に、特異的プライマーを用いたPCRによりC. racemosaと近縁植物を区別するARMS法を確立した。7種のサラシナショウマ属植物を用いた検討では、ARMS法によりC. racemosaとそれ以外の種を正しく判別することができた。同様に、国内市場で流通するブラックコホシュ製品の基原鑑別を行った結果、8製品のうち2製品には近縁種が使用され1製品にはサラシナショウマ属植物は含まれないことが明らかになった。さらに、国内市場品16製品に対して行ったTLC及びHPLCによる指標成分分析の結果は、ARMS法による鑑別結果とよく一致した。以上の結果より、植物組織を含むブラックコホシュ製品の基原鑑別において、ARMS法は有用であると考えられた。

著者

堀井 周文 小此木 明 高橋 隆二 鎌倉 浩之 袴塚 高志 合田 幸広

出版者

一般社団法人 日本生薬学会

雑誌

生薬学雑誌 (ISSN:13499114)

巻号頁・発行日

vol.74, no.1, pp.46-57, 2020-02-20 (Released:2021-03-11)

参考文献数

29

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Our previous studies [Horii, C., et al., Shoyakugaku Zasshi, 68(1), 9-12 (2014); Shoyakugaku Zasshi, 69(2), 59-65 (2015); Shoyakugaku Zasshi, 68(2), 65-69, (2014); Shoyakugaku Zasshi, 73(2), 73-83 (2019)], in which bioequivalence between the Kakkonto /Shoseiryuto decoction and its extract preparation was evaluated, revealed that some components can be marker compounds for bioequivalence but not others. In this study, we selected Hachimijiogan containing benzoylmesaconine, benzoylhypaconine, and 14-anisoylaconine specified as marker compounds by the Japanese Pharmacopoeia for quantification for quality control, and evaluated these components as possible marker compounds for bioequivalence.Six healthy adult males were randomly divided into two groups, and an oral administration crossover study was performed. Changes in the plasma concentrations of 10 components (benzoylmesaconine, benzoylhypaconine, 14-anisoylaconine, alisol A, alisol A monoacetate, alisol B, alisol B monoacetate, loganin, morroniside, and paeoniflorin) were evaluated. As a result, the plasma concentration of each component in both the decoction and extract preparation varied among blood collection sites. A t-test revealed a significant difference (p<0.01) in the plasma concentration of benzoylhypaconine 4 h after administration, a significant difference (p<0.05) in the plasma concentration of alisol A monoacetate 1 h after administration, and a significant difference (p<0.05) in the plasma concentration of loganin 4 h after administration, for the decoction and the extract. However, significant differences in the plasma concentrations of other constituents were not noted for the decoction and extract.Alisol B and alisol B monoacetate could not be quantified due to an inadequate SN ratio (SN rate 10 or more). Analysis of variance for 8 components after excluding alisol B and alisol B monoacetate showed a significant difference (p<0.05) in the area under the blood concentration-time curve (AUC0-8) for benzoylmesaconine in the subjects’ neck. The preparation, time and subjects did not differ significantly as a factor, so the statistical power (1-β) was calculated (except for alisol B and alisol B). Both the peak plasma concentration (Cmax) and AUC0-8 values for all 8 components had inadequate (< 80%) statistical powers (1-β).Next, the number of subjects needed to achieve sufficient statistical power was estimated based on the obtained results. The statistical powers of both Cmax and AUC0-8 were adequate (≧ 80%) when the number of subjects (1 group) was ≧ 24 (1 group) for benzoylmesaconine, ≧ 25 for 14-anisoylaconine, and ≧ 24 for alisol A. On the other hand, the statistical power was inadequate even when the number of subjects was 61 (1 group) for benzoylhypaconine, alisol A monoacetate, loganin, paeoniflorin, or morroniside.The contents of alisols have been reported to vary in Alisma Tuber. Considering conversion due to metabolism, alisol A is also difficult to use as a marker compound. Therefore, in this prescription, benzoylmesaconine and 14-anisoylaconine may be appropriate marker compounds.

著者

小田口 浩 日向 須美子 関根 麻理子 中森 俊輔 竹元 裕明 黄 雪丹 大嶋 直浩 嶋田 典基 楊 金緯 天倉 吉章 日向 昌司 内山 奈穂子 小林 義典 袴塚 高志 合田 幸広 花輪 壽彦

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.139, no.11, pp.1417-1425, 2019-11-01 (Released:2019-11-01)

参考文献数

21

被引用文献数

8 13

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Ephedra Herb is defined in the 17th edition of the Japanese Pharmacopoeia (JP) as the terrestrial stem of Ephedra sinica Stapf., Ephedra intermedia Schrenk et C.A. Meyer, or Ephedra equisetina Bunge (Ephedraceae). The stems of Ephedra Herb contain greater than 0.7% ephedrine alkaloids (ephedrine and pseudoephedrine). Despite its high effectiveness, Ephedra Herb exert several adverse effects, including palpitation, excitation, insomnia, and dysuria. Both the primary and adverse effects of Ephedra Herb have been traditionally believed to be mediated by these ephedrine alkaloids. However, our study found that several pharmacological actions of Ephedra Herb were not associated with ephedrine alkaloids. We prepared an ephedrine alkaloid-free Ephedra Herb extract (EFE) by eliminating ephedrine alkaloids from Ephedra Herb extract (EHE) using ion-exchange column chromatography. EFE exerted analgesic, anti-influenza, and anticancer activities in the same manner as EHE. Moreover, EFE did not induce adverse effects due to ephedrine alkaloids, such as excitation, insomnia, and arrhythmias, and showed no toxicity. Furthermore, we evaluated the safety of EFE in healthy volunteers. The number of adverse event cases was higher in the EHE-treated group than in the EFE-treated group, although the difference was not significant. Our evidence suggested that EFE was safer than EHE.

著者

袴塚 高志 鎌倉 浩之 渡辺 淳子 香取 征典 松本 和弘 石丸 順之 諸田 隆 合田 幸広

出版者

一般社団法人 日本生薬学会

雑誌

生薬学雑誌 (ISSN:13499114)

巻号頁・発行日

vol.74, no.2, pp.89-97, 2020-08-20 (Released:2021-09-08)

参考文献数

7

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Dry extract preparations of Kampo medicines for prescription were approved for use approximately 40 years ago in Japan. Presently, most Kampo medicines are prepared in the form of granules with a few being prepared as tablets or capsules. Granule formulations are generally unsuitable for the elderly due to their bulky nature. Although patients and Kampo manufacturers have expressed a need for the introduction of more acceptable granule alternatives, their introduction has been a challenge due to the lack of guidelines based on bioequivalence evaluations for medicines that include multiple chemical components. For resolving this issue, the researchers at the National Institute of Health Sciences initiated a study in 2009 funded by the Ministry of Health, Labour and Welfare. Several ingredients in Kampo extract products and corresponding standard decoctions were detectable and measurable in human plasma, and some compounds have been reported to be promising candidates for application in bioequivalence evaluations of Kampo formulations. The purpose of the present study was to investigate the potential to assess bioequivalence between kakkonto extract granules and tablets on the basis of the “Guidelines for Bioequivalence Testing of Generic Drugs (partial revision, PFSB/ELD Notification No. 0229010 dated February 29, 2012).”We investigated the pharmacokinetics of ephedrine and pseudoephedrine, which are ingredients derived from Ephedra Herba in kakkonto formulations, following the oral administration of kakkonto extract granules (one pack) and kakkonto extract tablets (eight tablets). The study was conducted as a two-group, two-period, and open-label crossover study in healthy Japanese volunteers. The plasma concentrations of ephedrine and pseudoephedrine following the administration of the drugs were measured using liquid chromatography with tandem mass spectrometry. Subsequently, we calculated their pharmacokinetic parameters and evaluated their bioequivalence. Analysis of variance using the area under the plasma concentration time curve (AUC) and the maximum plasma concentration (Cmax) of both ingredients revealed that while AUC indicated bioequivalence, Cmax values were significantly different. Plasma concentration levels in both formulations were similar in most volunteers and differed among some volunteers, which was attributed to a high number of tablets per dose as opposed to intra-individual variation. We concluded that ephedrine and pseudoephedrine in kakkonto extracts are good marker compounds for the evaluation of bioequivalence in different forms of kakkonto products. Our results suggest that the marker compounds exhibiting similarity in pharmacokinetic parameters following the administration of Kampo extract granules and the corresponding standard decoction could be applied as markers for the evaluation of bioequivalence between already-approved Kampo extract granules and novel Kampo products based on the same extract as that of granules.

著者

合田 幸広 袴塚 高志

出版者

一般社団法人 日本医薬品情報学会

雑誌

医薬品情報学 (ISSN:13451464)

巻号頁・発行日

vol.11, no.4, pp.210-216, 2010-03-31 (Released:2010-08-10)

参考文献数

4

著者

袴塚 高志

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.47, no.5, pp.413-418, 2011

著者

袴塚 高志

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.57, no.2, pp.99-103, 2021 (Released:2021-02-01)

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日本の生薬・漢方製剤の安全性,有効性及び品質は,公定書(日本薬局方及び局外生規[日本薬局方外生薬規格])を基礎として,GMP(Good Manufacturing Practice),GQP(Good Quality Practice),GVP(Good Vigilance Practice),GACP(Good Agricultural and Collection Practice)などにより多面的に確保され,各事業者が実施するべき個別の要件は製造販売承認書に規定されている.本稿では,現代日本の薬事制度において承認を受けた天然物医薬品としての生薬に限定して,その品質確保に資する取り組みについて主に制度の面から解説する.

著者

緒方 潤 河村 麻衣子 袴塚 高志 花尻(木倉) 瑠理

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.12, pp.1501-1508, 2020-12-01 (Released:2020-12-01)

参考文献数

18

被引用文献数

3

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In Japan, mitragynine, 7-hydroxymitragynine and Mitragyna speciosa Korth. (M. speciosa, “Kratom”) were controlled as Designated Substances under the Pharmaceutical and Medical Device Act from March 2016. In this study, the origins of 16 Kratom products obtained from the illegal drug market in Japan were investigated by DNA analyses and LC-MS analyses. When the PCR-restriction fragment length polymorphism (RFLP) was performed using the restriction enzyme XmaI (as reported by Sukrong et al. to be able to distinguish M. speciosa), the same DNA fragment patterns were obtained from all 16 products. On the other hand, as a result of the identification of the plant species of each product by nucleotide sequence analyses, the sequences of M. speciosa were detected in only 14 products. Despite the facts that mitragynine and 7-hydroxymitragynine were detected also in the other two products by the LC-MS analyses, M. speciosa DNAs were not amplified from these products by the PCR. Moreover, the DNA amplicons of the other psychotropic plant (Mesembryanthemum sp., e.g. “Kanna”) were detected. This plant PCR amplicon has the restriction site for the XmaI at the same position of the M. speciosa PCR amplicon and it is difficult to distinguish “Kratom” and “Kanna” by the conventional PCR-RFLP. When the restriction enzyme XhoI was used simultaneously with the Xmal, the specific DNA fragment was only observed from the M. speciosa amplicon and it was possible to distinguish both species using this improved PCR-RFLP method. This method is useful to identify the origin of Kratom products distributed in the illegal drug market.

著者

袴塚 高志

出版者

東京大学

巻号頁・発行日

1992

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博士論文