著者

内山 奈穂子 花尻(木倉) 瑠理

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.52, no.9, pp.855-859, 2016 (Released:2016-09-02)

参考文献数

26

被引用文献数

1

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2011年頃から,危険ドラッグが関与したと考えられる健康被害や自動車事故等の他害事件の報告が急増し,大きな社会問題となった.2016年4月時点で,医薬品医療機器等法下,指定薬物として規制されている物質数は2,343物質であるが,その中でカンナビノイド受容体に対し作用を有する合成物質群(合成カンナビノイド)の数は最も多く,全体の約40%を占める(包括指定を除く).本稿では,合成カンナビノイドの流通実態およびその法規制について解説する.

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

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

花尻(木倉) 瑠理 内山 奈穂子 河村 麻衣子 緒方 潤 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.133, no.1, pp.31-40, 2013 (Released:2013-01-01)

参考文献数

30

被引用文献数

14 26

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In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category; Designated Substances in order to more strictly control these substances. In April 2007, 31 compounds and 1 plant were first controlled as Designated Substances. Before 2007, the major compounds distributed in the Japanese illegal drug market were tryptamines, phenethylamines and piperazines. Alkyl nitrites, such as isobutyl nitrite and isopentyl nitrite, were also widely distributed. After they were listed as Narcotics or Designated Substances in 2007, these compounds, especially the tryptamines, quickly disappeared from the market. In their place, cathinone derivatives have been widely distributed, as well as different phenethylamines and piperazines. Additionally, in recent years, new herbal products containing synthetic cannabinoids have appeared globally. As at July 2012, 78 substances (including 1 plant; Salvia divinorum) were listed in the category of Designated Substances. They were 13 tryptamines, 17 phenethylamines, 11 cathinones, 4 piperazines, 23 synthetic cannabinoids, 6 alkyl nitrites, 3 other compounds and 1 plant. In this review, we show our survey of the spread of new designer drugs in Japan, focusing especially on synthetic cannabinoids and cathinone derivatives. Also, the prevalence and legal status of these substances in other countries will be presented.

著者

内山 奈穂子 宮澤 法政 河村 麻衣子 花尻(木倉) 瑠理 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.130, no.2, pp.263-270, 2010-02-01 (Released:2010-02-01)

参考文献数

18

被引用文献数

14 16

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Thirty-two psychotropic substances were listed as designated substances (Shitei-Yakubutsu, 31 compounds and 1 plant) in Japan by the Pharmaceutical Affairs Law in April 2007 for preventing the abuse of these substances. Subsequently, other psychoactive compounds were also added to this category, 40 substances (classified as 12 tryptamines, 17 phenethylamines, 3 piperazines, 6 alkyl nitrites, 1 diterpene and 1 plant) are controlled as designated substances as of July 2009. However, new designer drugs are still distributed in illegal drug market according to the results of our annual survey. This study presents the analysis of four newly distributed designer drugs detected from two products, which were purchased from October 2008 to February 2009 in Japan. As the results of NMR, GC-MS and LC-MS analyses, three phenethylamine derivertives, 1-(2-fluorophenyl)-N-methylpropan-2-amine (N-Me-2-FMP), 1-(2,5-dimethoxy-4-isopropylsulfanylphenyl)propan-2-amine (ALEPH-4) and 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine (DON) and a tryptamine derivative, N-ethyl-5-methoxy-N-propyltryptamine (5-MeO-EPT), were detected. N-Me-2-FMP and 5-MeO-EPT were newly identified in this study. Additionally, ALEPH-4 and DON were found as novel illegal drugs distributed in Japan.

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

内山 奈穂子 花尻(木倉) 瑠理 正田 卓司 福原 潔 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.131, no.7, pp.1141-1147, 2011-07-01 (Released:2011-07-01)

参考文献数

12

被引用文献数

11 12

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Recently, many psychotropic herbal products, named such as “Spice”, were distributed worldwide via the Internet. In our previous study, several synthetic cannabinoids were identified as adulterants in herbal products being available in Japan due to their expected narcotic effects. Among those, two derivatives of Δ9-tetrahydrocannabinol (Δ9-THC), which is major psychotropic cannabinoid of marijuana, cannabicyclohexanol (CCH, 3-[2-hydroxy-4-(2-methylnonan-2-yl)phenyl]cyclohexan-1-ol) and CP-47,497 (3-[2-hydroxy-4-(2-methyloctan-2-yl)phenyl]cyclohexan-1-ol), have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law since November 2009. CCH was detected together with its trans-form (1-epimer) in many herbal products, and CCH and CP-47,497 have two chiral centers in the structures. However, the pharmaceutical activities of the isomers of CCH have not been reported. This study presents chiral separations of CCH, its trans-form and CP-47,497 in the products using LC-circular dichroism (CD) and LC-MS analyses. The enantiomeric pairs of CCH, its trans-form and CP-47,497 were separated, respectively. Subsequently, the analyses of the herbal products showed that CCH and its trans-form existed as mixtures of enantiomers and the relative ratios of CCH and the trans-form enantiomers ranged from 42/58% to 53/47% and from 33/67% to 52/48%, respectively.

著者

内山 奈穂子 有竹 浩介 マリシェフサカヤ オリガ

出版者

国立医薬品食品衛生研究所

雑誌

基盤研究(C)

巻号頁・発行日

2016-04-01

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大麻由来カンナビノイドΔ9-THC或いは合成カンナビノイド(JWH-018)を投与したマウスの脳波と自発運動量の変化を調べた.マウスにΔ9-THCを腹腔内投与すると,有意な行動量の低下が観察され,痙攣行動と痙攣脳波が誘発され,痙攣脳波は断続的に4時間以上持続して起こることが判明した.一方,JWH-018を腹腔内投与すると,Δ9-THCと比較して,行動量の抑制と痙攣がより投与から短時間に誘発されることが判明した.さらに,JWH-018によるマウスへの痙攣誘発作用が容量依存的に起こることが明らかとなった.また,CB1受容体選択的拮抗薬AM251をΔ9-THC 或いはJWH-018投与の30分前に腹腔内投与しておくと,行動量の抑制と痙攣の誘発が完全に消失することが判明した.従って,Δ9-THCやJWH-018は,CB1受容体を介してマウスに痙攣を誘発することが示された.次に,痙攣を誘発するΔ9 -THC用量の閾値を検討した結果,投与量2.5 mg/kgが痙攣を誘発する最低用量であった.さらに,脳波スペクトルの特性を視覚的に区別することができる脳波解析:スペクトログラムとエンベロープ変動係数解析を行った.さらに,Δ9-THCの反復投与により,投与3-4日後に痙攣の発生数が減少したことから,Δ9-THC連続投与により身体的な耐性が生じることが示された.また,CB1受容体拮抗薬をマウスに前投与することにより,Δ9-THCおよびJWH-018によって誘発される痙攣が抑制されたことから,これらの痙攣作用は,CB1受容体を介して起こることが示された.さらにCB1受容体KOマウスにJWH-018を腹腔投与した結果,CB1受容体KOマウスはJWH-018投与後に痙攣の脳波または痙攣行動を示さなかったことから,JWH-018の痙攣作用は,CB1受容体を介して起こることが改めて確認された.