著者

下村 裕子 徳本 廣子 関田 節子 佐竹 元吉 徳川 斉正 徳川 眞木 合田 幸広

出版者

日本生薬学会

雑誌

生薬學雜誌 : shoyakugaku zasshi : the Japanese journal of pharmacognosy (ISSN:13499114)

巻号頁・発行日

vol.67, no.2, pp.41-58, 2013-08-20

参考文献数

79

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The gallipot found as the heirloom of the Mito-Tokugawa family has the unclear label "Usaien" and contains a small amount of dry black preparation. It is historically clear that Ieyasu Tokugawa, who was the founder of the Edo Shogunate, used it. Fortunately, the "Korean Wazaikyokuho", which was a formulary of natural medicines, has been found as one of the valuable possessions of Kunozan Toshogu, where Ieyasu Tokugawa is enshrined and the formulary contains the "Usaien" formula. It is of interest to reveal the components of the preparation from the viewpoints of historiography and pharmacognosy. Therefore, by utilizing the "Usaien" formula as a clue, we started microscopic analyses to reveal the crude drug components of the historical dry black preparation. First we found this preparation contained a lot of pollens which were thought to be of multiple origins. This indicated the preparation was a kind of honey paste. Furthermore, the successive analyses on the basis of the morphological characteristics of elements of the crude drugs led to the identification of 52 crude drugs (herbal origins: 35, animal origins: 14 and minerals: 3) as the components. The reference formula in the "Korean Wazaikyokuho" consisted of 58 crude drugs and of them 2 volatile ones, 2 sarcous ones, mercury and calomel have remained unidentified, because of difficulty of confirmation by microscopic analyses or insufficient information the origin of their crude drugs. Since most of the crude drug components of the "Usaien" formula were identified in the dry black preparation, we thought the shogun, Ieyasu Tokugawa, used the formula for his health care.

著者

合田 幸広 酒井 信夫 中村 高敏 穐山 浩 豊田 正武

出版者

Japanese Society for Food Hygiene and Safety

雑誌

食品衛生学雑誌 (ISSN:00156426)

巻号頁・発行日

vol.39, no.4, pp.256-265_1, 1998-08-05 (Released:2009-12-11)

参考文献数

22

被引用文献数

5 12

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日本で栽培されているモロヘイヤの種子中の主強心配糖体の単離構造決定を行い, strophanthidin 配糖体 (erysimoside, olitoriside, corchoroside A, helveticoside), だけでなく, digitoxigenin 配糖体 (coroloside, glucoevatromonoside) も含まれていることも明らかにした. また, HPLCによる分析から, モロヘイヤの種子には, これらの化合物が種子湿重量の0.1~1%存在し, 種子の色の違いによって, 強心配糖体の含有量及び組成が異なることを示した. 精製した強心配糖体 erysimoside+olitoriside, 及び coroloside+glucoevatromonoside を, ddY系雄性マウスに対し経口投与した結果, 両者とも500mg/kg以上のLD50値を示した.

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

花尻(木倉) 瑠理 丸山 卓郎 宮下 聡徳 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.129, no.8, pp.975-982, 2009-08-01 (Released:2009-08-01)

参考文献数

23

被引用文献数

11 12

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Voacanga africana (Apocynaceae) is a small tropical African tree. The root bark and seeds of this tree contain a number of alkaloids, including ibogaine (a hallucinogenic/aphrodisiac compound in bark), tabersonine (a major constituteent of seeds) and other voacanga alkaloids, traditionally used in Africa for religious purposes. Recently, some kinds of products containing this plant (root bark and seeds) have been distributed in the drug market in expectation of its hallucinogenic/aphrodisiac effects. There has been no report that has discussed quantitative analyses of these alkaloids in the products and their botanical origins. In this study, to investigate the trend of such a non-controlled psychotropic plant of abuse, a simultaneous analytical method was developed using LC/MS for the voacanga alkaloids including ibogaine and tabersonine in the commercial products of V. africana. Moreover, the botanical origins of these products were investigated by DNA analyses. As a result of the LC/MS analyses, the products were classified into two chemical types; an ibogaine-type and a tabersonine-type. The samples of the ibogaine-type contain ibogaine (0.05-0.6%) and other voacanga alkaloids; voacamine, voacamidine and voacangine, while those of the tabersonine-type mainly contain tabersonine (0.6-1.6%). The sequence analyses of chloroplast DNA, trnL-F region suggested that most of the products were derived from V. africana or closely related plants. They were classified into four genotypes based on nucleotide sequence of the trnL-F IGS region. The proposed methods of chemical and DNA analyses would be useful for investigating the trend in the distribution of the products of V. africana.

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

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

合田 幸広

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.75, no.3, pp.170-176, 2015 (Released:2015-11-01)

参考文献数

5

被引用文献数

2

著者

川原 信夫 酒井 英二 糸数 七重 佐竹 元吉 合田 幸広

出版者

日本生薬学会

雑誌

生薬學雜誌 (ISSN:13499114)

巻号頁・発行日

vol.60, no.1, pp.39-50, 2006-02-20

被引用文献数

4

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本研究は食肉の風味を形成する食感, 味, 香りについて次の新知見を加えたものである。食肉の熟成による軟化の主原因の一つとみられるアクチン・ミオシン構造体のゆるみ現象が, 筋原線維のMg-ATPase 活性のKCl濃度依存性と最大活性値の増大となって観察されることを示し, おのおのが筋肉酵素カテプシンB, D, H, L, の共同作用とグリセルアルデヒド-3-リン酸脱水素酵素の筋原線維への不可逆的結合で起こることを明らかにした。これに際し, 骨格筋カテプシンB, D, Hの高純度精製法を確立した。カテプシンLは新規酵素として発見したもので, 他所で同時期に発見された肝臓の新規酵素との類似性から, 両酵素はカテプシンLと命名された。食肉の熟成中に遊離アミノ酸が増加し, 味と加熱香気の向上に寄与する。この遊離アミノ酸の増加はおもに筋肉中性アミノペプチダーゼ類の作用によることを示し, 4個以上のアミノ酸からなるペプチドはおもに新たに発見したアミノペプチダーゼCとHの共同作用によって分解されることを明らかにした。わが国では黒毛和牛の脂肪が赤身によく交雑した霜降り肉が最もおいしいと評価されている。その主原因は該牛肉を酸素共存下で熟成後, 加熱することで生成する脂っぽい甘い芳香 (和牛香と命名) であることを示し, 本香を構成する香気成分を明らかにした。各種の食肉を食したときの畜種の判別に寄与する官能的主因子は香りであり, 味の寄与はきわめて小さいことを示した。

著者

近藤 一成 穐山 浩 合田 幸広 豊田 正武

出版者

公益社団法人 日本食品衛生学会

雑誌

食品衛生学雑誌 (ISSN:00156426)

巻号頁・発行日

vol.38, no.6, pp.412-417_1, 1997-12-05 (Released:2009-12-11)

参考文献数

12

被引用文献数

2

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モロヘイヤ (C. olitorius) の各部位及び野菜“モロヘイヤ”, モロヘイヤ加工品である健康茶及び健康食品中の強心配糖体の分析法を開発した. 試料のメタノール抽出液を1mol/L塩酸で加水分解後, 種子は直接, その他の試料は Silica gel カラムで前処理し, 逆相HPLCでストロファンチジン (SP) として分析した. 完熟種子中には強心配糖体がSPとして平均5.43mg/g, その莱には0.24μg/g含まれていたが, 茎, 野菜“モロヘイヤ”, モロヘイヤ加工品である健康茶及び健康食品中には強心配糖体は含まれていなかった. したがって, 日常の食生活に用いられるモロヘイヤ中には強心配糖体は存在しないものと考えられる. また, 完熟種子にはSPをアグリコンとし, 糖部の異なる少なくとも2種の強心配糖体が存在することが明らかになった.

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

小笠原 健 荒川 史博 穐山 浩 合田 幸広 小関 良宏

出版者

Japanese Society of Food Chemistry

雑誌

日本食品化学学会誌 (ISSN:13412094)

巻号頁・発行日

vol.10, no.3, pp.155-160, 2003-12-12 (Released:2017-12-01)

参考文献数

19

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さまざまな大豆加工食品における組換え遺伝子の音量とDNA断片化の程度を調べることにより、厚生労働省により通知された公定法記載の定量PCR法の加工食品への適用可能性について検証した。豆腐のように100℃程度で加熱加工された場合は、適用できることがわかった。しかし、市販されている加工食品のように加熱され、物理的力が更にかかるオートクレーブ処理などが行われた場合、あるいは発酵食品の場合、100bp程度までDNAの厳しい断片化が引き起こされることが明らかとなった。従って、これらの加工食品中の遺伝子組換え大豆の定量を行うには95bpより短いプライマー、プローブを開発する必要があると考えられた。

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

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

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.134, no.2, pp.197-202, 2014-02-01 (Released:2014-02-01)

参考文献数

9

被引用文献数

1 1

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With the prefectural governments' aid of the purchase, the Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences (NIHS) successively has surveyed illegal constituents in health food products implicitly advertizing tonic or slimming effect since the fiscal year of 2002 (slimming type) or 2003 (tonic type). The average numbers of the analyzed products per year are about 100 (slimming type) and 150 (tonic type), respectively. We also continuously distribute standards of authentic samples of several illegal components such as N-nitrosofenfluramine (NFF) and sildenafil (SIL) to prefectural institutes and the average gross number per year is about 140. In the case of slimming type, the fact that the products containing NFF were widely sold in Japanese markets in 2002 is well known. In addition, phenolphthalein, fenfluramine, sibtramine, desdimethylsibtramine, orlistat, mazindol, Rhubarb, Senna Leaf, etc. have been found as illegal constituents. In the tonic type products, we have identified more than 20 synthetic compounds relating to the erectile dysfunction (ED) treatment drugs, SIL, vardenafil and tadalafil (TDF). Since 2005, their synthetic intermediates and the patented but non-approved PDE5 inhibitors also have been found. It should be noted that TDF was found in the shells of capsule in 2009 and that mutaprodenafil was found as pro-drug type illegal component in 2010. In this report identification method of these illegal constituents is briefly described and then analytical trend in this decade is reviewed.

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

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

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.141, no.6, pp.787-791, 2021-06-01 (Released:2021-06-01)

参考文献数

11

被引用文献数

3

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The author believes that the three pillars of pharmaceutical sciences (PS) in Japan are drug development science, medical pharmacy, and quality management science. Of these, the most PS-like science is quality management science, both historically and presently. Considering the balance of safety and efficacy is the basis of PS. The definition of “quality” is the degree to which a set of inherent properties of a product, system, or process fulfills requirements in Q9 of International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). In our society, pharmaceutical science graduates including pharmacists, are active participants, not only in the pharmaceutical industry, including a pharmacy, but also in the food industry, especially for quality assurance and quality control. This report presents a focused overview of quality in health foods, foods with health claims, and pharmaceutical products and discusses the importance of a curriculum focusing on quality assurance, control, and management in pharmaceutical education.

著者

ガン エン 松藤 寛 千野 誠 合田 幸広 豊田 正武 武田 明治

出版者

公益社団法人 日本食品衛生学会

雑誌

食品衛生学雑誌 (ISSN:00156426)

巻号頁・発行日

vol.42, no.5, pp.298-303, 2001-10-25 (Released:2009-03-25)

参考文献数

11

被引用文献数

2 4

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市販食用緑色3号(主色素:HSBA-(m-EBASA) (m-EBASA), m,m-G-3)に含まれる付随色素について,高速液体クロマトグラフを用いて分析したところ,8つの付随色素の存在が確認された.それらの中で,4つの付随色素(付随色素 C, F, G, H)を精製単離し,質量分析計並びに核磁気共鳴分光計を用いて構造決定した.付随色素Cはm,p-G-3, 付随色素FはHSBA-(ethylaniline: EA)(m-EBASA), 付随色素Gは HSBA-(di-EA) (m-EBASA), 付随色素Hは HSBA-(ethylbenzylaniline: EBA)(m-EBASA)であった.付随色素Gは,これまでに報告例のない新規な付随色素であった.