著者

柏田 良樹 森田 益史 野中 源一郎 西岡 五夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.4, pp.856-860, 1990-04-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

11 15

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A chemical examination of the polyphenolic constituents of the fern, Dicranopteris pedata HOUTT., has led to the isolation of eight new proanthocyanidins possessing a doubly-linked (A-type) unit, together with known flavan-3-ols and proanthocyanidins. On the basis of chemical and spectroscopic evidence, they are characterized as epiafzelechin-(4β→8, 2β→O→7)-eniafzelechin-(4α→8)-epiafzelechin(8), epicatechin-(4β→8, 2β→O→7)-epiafzelechin-(4α→8)-epiafzelechin(9), epiafzelechin-(4β→8, 2β→O→7)-epizfzelechin-(4α→8)-epicatechin(10), epiafzelechin-(4β→8, 2β→O→7)-epicatechin-(4α→8)-epicatechin (11), epicatechin-(4β→8, 2β→O→7)-epiafzelechin-(4α→8)-epicatechin (12), epicatechin-(4β→8, 2β→O→7)-epicatechin-(4α→8)-epiafzelechin (13), epicatechin-(4β→8, 2β→O→7)-epicatechin-(4α→8)-epigallocatechin (14) and epiafzelechin-(4β→8)epicatechin-(4β→8, 2β→O→β→7)-epicatechin-(4α→8)-epicatechin (15).

著者

Shadi Sedghi Masoud Kazuo Nagasawa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.12, pp.1091-1103, 2018-12-01 (Released:2018-12-01)

参考文献数

112

被引用文献数

14 43

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The i-motif is a high-order DNA structure formed by hemiprotonated cytosine–cytosine base pairs under acidic conditions. It is less well studied than other high-order DNA structures, such as G-quadruplexes. However, increasing numbers of i-motif-binding ligands are being reported, and they are being used as tools to investigate the i-motif’s structure and biological functions. It has become clear that the i-motif has a functional role in the regulation of gene expression. In this review, we provide an overview of i-motif ligands so far reported, and we summarize their effects on the structure and their use as tools to investigate its biological functions.

著者

Wei Peng Yan-Yan Ma Kun Zhang Ai-Yu Zhou Yu Zhang Huaqian Wang Zhiyun Du Deng-Gao Zhao

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.64, no.6, pp.609-615, 2016-06-01 (Released:2016-06-01)

参考文献数

18

被引用文献数

9 14

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Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol–ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases.

著者

Hayato Ishimoto Manabu Kano Hirokazu Sugiyama Hirofumi Takeuchi Katsuhide Terada Atsushi Aoyama Takuji Shoda Yosuke Demizu Jinen Shimamura Reiji Yokoyama Yuji Miyamoto Koji Hasegawa Masaru Serizawa Kazuomi Unosawa Kazuo Osaki Naochika Asai Yoshihiro Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.2, pp.211-217, 2021-02-01 (Released:2021-02-01)

参考文献数

27

被引用文献数

3

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As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.

著者

大場 節哉 今野 昌悦 山中 宏

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.2, pp.486-488, 1991-02-25 (Released:2008-03-31)

参考文献数

25

被引用文献数

19 33

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A cyano group in 1, 2, 4-triaznes, regardless of its position, acted as an effective leaving group in reactions with carbanions. Thus, the reactions gave the corresponding substituted products in place of the compounds formed by addition reaction of carbanions to the cyano group. Grignard reaction of these carbonitriles is also described.

著者

Hayato Ishimoto Manabu Kano Hirokazu Sugiyama Hirofumi Takeuchi Katsuhide Terada Atsushi Aoyama Takuji Shoda Yosuke Demizu Jinen Shimamura Reiji Yokoyama Yuji Miyamoto Koji Hasegawa Masaru Serizawa Kazuomi Unosawa Kazuo Osaki Naochika Asai Yoshihiro Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c20-00824, (Released:2020-12-08)

参考文献数

27

被引用文献数

3

---

As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.

著者

Magie Melanie Kapojos Delfly Booby Abdjul Hiroyuki Yamazaki Akiho Yagi Ryuji Uchida

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.9, pp.903-906, 2020-09-01 (Released:2020-09-01)

参考文献数

14

被引用文献数

1

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Bioassay screening using Indonesian plants, such as traditional foods (vegetables, spices, and tea) and folk medicinal herbs, identified eight protein tyrosine phosphatase (PTP) 1B inhibitory and two antibacterial plants. The leaves of Syzygium polyanthum (Wight) Walp. were examined in more detail to define PTP1B inhibitory components, resulting in the isolation of a new active acylbenzene (1) along with four related congeners of 1 (2–5) and four oleanane triterpenes (6–9). The structure of 1 was elucidated as 12-oxo-12-(2,3,5-trihydroxy-4-methylphenyl)dodecanoic acid based on its spectroscopic data. The acylbenzenes 1 and 3–5 inhibited PTP1B activity with IC50 values ranging between 9.5 and 14 µM, whereas the triterpenes 7–9 also suppressed this activity with IC50 values of 3.3–5.7 µM.

著者

本橋 範子 西川 晴美 森 五彦

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.39, no.1, pp.142-145, 1991-01-25 (Released:2008-03-31)

参考文献数

26

被引用文献数

3 5

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The inhibitory effects of sulfur compounds, namely cysteine and α-mercaptopropionylglycine (α-MPG) (thiol type), and N-methyl-3-mercaptoimidazole (MMI), 6-propylthiouracil (PTU) and ergothioneine (ESH) (thione type) on melanin formation reaction by tyrosinase, in the presence of tyrosine as a substrate, were assessed. Tyrosine oxidation was monitored both by radioassay using L-[3, 5-3H]tyrosine, L-[2, 6-3H]tyrosine and L-[carboxyl-14C]tyrosine as substrates, and by spectrometry to quantitate the dopachrome formed from L-tyrosine. The rated compounds, ranked as to inhibitory effect in descending order are : cysteine ≃α-MPG>MMI>PTU>ESH. Cysteine and α-MPG, both noncyclic thiol compounds, formed a 3, 4-dihydroxyphenylalanine (dopa) conjugate to inhibit melanin formation when added at low concentrations. At high concentrations, they inctivated the enzyme by interacting with tyrosinase. In MMI, PTU and ESH of heterocyclic thione structure, dopa conjugate formation was more inhibitory than tyrosinase inactivation on melanin formation.

著者

Yasuhiro Abe Eiichi Yamamoto Hiroyuki Yoshida Akiko Usui Naomi Tomita Hitomi Kanno Sayaka Masada Hidetomo Yokoo Genichiro Tsuji Nahoko Uchiyama Takashi Hakamatsuka Yosuke Demizu Ken-ichi Izutsu Yukihiro Goda Haruhiro Okuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c20-00431, (Released:2020-08-08)

参考文献数

28

被引用文献数

20

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The purpose of this study was to elucidate the effect of high-temperature storage on the stability of ranitidine, specifically with respect to the potential formation of N-nitrosodimethylamine (NDMA), which is classified as a probable human carcinogen. Commercially available ranitidine reagent powders and formulations were stored under various conditions, and subjected to LC-MS/MS analysis. When ranitidine tablets from two different brands (designated as tablet A and tablet B) were stored under accelerated condition (40°C with 75% relative humidity), following the drug stability guidelines issued by the International Conference on Harmonisation (ICH-Q1A), for up to 8 weeks, the amount of NDMA in them substantially increased from 0.19 to 116 ppm and from 2.89 to 18 ppm, respectively. The formation of NDMA that exceeded the acceptable daily intake limit (0.32 ppm) at the temperature used under accelerated storage conditions clearly highlights the risk of NDMA formation in ranitidine formulations when extrapolated to storage under ambient conditions. A forced-degradation study under the stress condition (60°C for 1 week) strongly suggested that environmental factors such as moisture and oxygen are involved in the formation of NDMA in ranitidine formulations. Storage of ranitidine tablets and reagent powders at the high temperatures also increased the amount of nitrite, which is considered one of the factors influencing NDMA formation. These data indicate the necessity of controlling/monitoring stability-related factors, in addition to controlling impurities during the manufacturing process, in order to mitigate nitrosamine-related health risks of certain pharmaceuticals.

著者

Kensuke Yagi Keiichi Goto Fumio Nanjo

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.57, no.11, pp.1284-1288, 2009-11-01 (Released:2009-11-01)

参考文献数

21

被引用文献数

17 25

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The polyphenolic composition of Camellia irrawadiensis, which is a closely related species of Camellia sinensis (cultivated tea), was investigated. The most predominant polyphenol, a kind of ellagitannin, was isolated from leaves of C. irrawadiensis. Its structure was established as 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (2) on the basis of spectral and chemical evidence. Moreover, the polyphenols [catechins, strictinin (1), compound 2, theogallin, and gallic acid] and two methylxanthines (theobromine and caffeine) in leaves of C. irrawadiensis were determined by HPLC-Photodiode array detector analysis, and were compared to those in C. sinensis and Camellia taliensis. Total catechin content in C. irrawadiensis was lower than that in C. sinensis and C. taliensis. Theobromine content in C. irrawadiensis was higher than that in C. sinensis and C. taliensis. The content of 2 in C. irrawadiensis was 8.4% of dry leaf weight and comprised approximately 60% of the total polyphenols detected, while the compound was not detected in C. sinensis and was reported to be 2.4% in C. taliensis.

著者

Ryosuke Mitani Shuji Ohsaki Hideya Nakamura Satoru Watano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.8, pp.726-736, 2020-08-01 (Released:2020-08-01)

参考文献数

40

被引用文献数

10

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This study investigated the particle adhesion mechanism in a capsule of dry powder inhaler (DPI) based on a combined computational fluid dynamics and discrete element method (CFD–DEM) approach. In this study, the Johnson–Kendall–Roberts (JKR) theory was selected as the adhesion force model. The simulation results corroborated the experimental results—numerous particles remained on the outlet side of the capsule, while a few particles remained on the inlet side. In the computer simulation, the modeled particles were placed in a capsule. They were quickly dispersed to both sides of the capsule, by air fed from one side of the capsule, and delivered from the air inlet side to the outlet side of the capsule. It was confirmed that vortex flows were seen at the outlet side of the capsule, which, however, were not seen at the inlet side. Numerous collisions were observed at the outlet side, while very few collisions were observed at the inlet side. These results suggested that the vortex flows were crucial to reduce the amount of residual particles in the capsule. The original capsule was then modified to enhance the vortex flow in the area, where many particles were found remaining. The modified capsule reduced the number of residual particles compared to the original capsule. This investigation suggests that the CFD–DEM approach can be a great tool for understanding the particle adhesion mechanism and improving the delivery efficiency of DPIs.

著者

染井 正徳 加藤 恵子 井上 里美

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.8, pp.2515-2518, 1980-08-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

18 29

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An improved procedure which avoids prolonged reaction at high temperature and handling under reduced pressure was found for the reduction of heteroaromatic and aromatic nitro compounds with aqueous titanium (III) chloride.

著者

Sirada Boonyaketgoson Yongle Du Ana L. Valenciano Murillo Maria B. Cassera David G. I. Kingston Kongkiat Trisuwan

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.7, pp.671-674, 2020-07-01 (Released:2020-07-01)

参考文献数

17

被引用文献数

6

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Chromatographic separation of the acetone extracts from the twigs and barks of Artocarpus lakoocha led to the isolation of the one new flavanone, lakoochanone (1), together with eleven known compounds (2–12). Lakoochanone (1) and moracin C (4) exhibited weak antiplasmodial activity against Plasmodium falciparum Dd2 with IC50 values of 36.7 and 33.9 µM, respectively. Moreover, moracin C (4) and sanggenofuran B (5) showed cytotoxic activity against A2780 cell line with the respective IC50 values of 15.0 and 57.1 µM. In addition, cyclocommunin (7) displayed strong antimycobacterial activity against Mycobacterium tuberculosis H37Ra with the minimum inhibitory concentration (MIC) value of 12.3 µM.

著者

Koki Ogawa Naoya Kato Shigeru Kawakami

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.7, pp.567-582, 2020-07-01 (Released:2020-07-01)

参考文献数

187

被引用文献数

17

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Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood–brain barrier (BBB) or blood–brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to deliver therapeutic agents to the brain. Recently, brain-targeted DDS have been developed, which increases the quality of therapy for cerebral disorders. This review gives an overview of recent brain-targeting DDS strategies. First, it describes strategies to cross the BBB. This includes BBB-crossing ligand modification or temporal BBB permeabilization. Strategies to avoid the BBB using local administration are also summarized. Intrabrain drug distribution is a crucial factor that directly determines the therapeutic effect, and thus it is important to evaluate drug distribution using optimal methods. We introduce some methods for evaluating drug distribution in the brain. Finally, applications of brain-targeted DDS for the treatment of brain tumors, Alzheimer’s disease, Parkinson’s disease, and stroke are explained.

著者

西村 幸治 橋本 祐一 岩崎 成夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.42, no.5, pp.1157-1159, 1994-05-15 (Released:2008-03-31)

参考文献数

8

被引用文献数

57 73

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The rate of racemization of N(α)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37°C. This fast racemization of thalidomide resulted in no apparent difference between (S)- and (R)-forms of the compound on enhancing activity of phorbol ester-induced tumor necrosis factor (TNF)-α production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-α -methyl-N(α)-phthalimidoglutarimides (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-α production-enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.

著者

Satoki Aoki Takako Aboshi Yoshihito Shiono Ken-ichi Kimura Toshihiro Murata Daisuke Arai Yoshiaki Iizuka Tetsuya Murayama

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.5, pp.436-442, 2020-05-01 (Released:2020-05-01)

参考文献数

31

被引用文献数

6

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Six new sesquiterpenes, tsukiyols A–C, neoilludin C, and 4-O-methylneoilludins A and B, were isolated from the fruiting body of Omphalotus japonicus (Kawam.) Kirchm. & O. K. Mill. Additionally, six known compounds, illudin S, neoilludins A–B, 5-hydroxydichomitol, ergosterolperoxide, and 3β,5α,9α-trihydroxyergosta-7,22-diene-6-one, were also obtained. Their chemical structures were determined with MS, IR, and NMR spectra and the absolute configurations of neoilludins A–C, 4-O-methylneoilludins A, and B were determined with electronic circular dichroism (ECD). Illudin S and 3β,5α,9α-trihydroxyergosta-7,22-diene-6-one showed cytotoxicity against human acute promyelocytic leukemia HL60 cells. Illudin S, 4-O-methylneoilludin A, B, and tsukiyol C showed growth-restoring activity against mutant yeast via Ca2+-signal transduction.

著者

Toshio Morikawa Hideo Oominami Hisashi Matsuda Masayuki Yoshikawa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.58, no.11, pp.1541-1544, 2010-11-01 (Released:2010-11-01)

参考文献数

37

被引用文献数

12 20

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Four new ursane-type triterpenes, olibanumols K (1), L (2), M (3), and N (4), were isolated from traditional Egyptian medicine olibanum, the exuded gum-resin from Boswellia carterii BIRDW. Their structures were elucidated on the basis of chemical and physicochemical evidence.

著者

Naohiro Oshima Honoka Kume Takayoshi Umeda Haruki Takito Mitsutoshi Tsukimoto Noriyasu Hada

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.1, pp.91-95, 2020-01-01 (Released:2020-01-01)

参考文献数

34

被引用文献数

5

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Magnolia Flower is a crude drug used for the treatment of headaches, toothaches, and nasal congestion. Here, we focused on Magnolia kobus, one of the botanical origins of Magnolia Flower, and collected the flower parts at different growth stages to compare chemical compositions and investigate potential inhibitory activities against interleukin-2 (IL-2) production in murine splenic T cells. After determining the structures, we examined the inhibitory effects of the constituents of the bud, the medicinal part of the crude drug, against IL-2 production. We first extracted the flower parts of M. kobus from the bud to fallen bloom stages and analysed the chemical compositions to identify the constituents characteristic to the buds. We found that the inhibitory activity of the buds against IL-2 production was more potent than that of the blooms. We isolated two known compounds, tiliroside (1) and syringin (2), characteristic to the buds from the methanol (MeOH) extract of Magnolia Flower. Moreover, we examined the inhibitory activities of both compounds against IL-2 production and found that tiliroside (1) but not syringin (2), showed strong inhibitory activity against IL-2 production and inhibited its mRNA expression. Thus, our strategy to examine the relationship between chemical compositions and biological activities during plant maturation could not only contribute to the scientific evaluation of medicinal parts of crude drugs but also assist in identifying biologically active constituents that have not yet been reported.

著者

Hiromitsu Takayama

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.2, pp.103-116, 2020-02-01 (Released:2020-02-01)

参考文献数

67

被引用文献数

8

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The merits of biogenetic considerations in the chemical syntheses of natural products have been emphasized by describing the total syntheses of Lycopodium alkaloids; lycodine, flabellidine, lycopodine, and flabelliformine, as well as monoterpenoid indole alkaloids; C-mavacurine, kopsiyunnanine K, koumine, and 11-methoxy-19R-hydroxygelselegine.

著者

Wei Peng Yan-Yan Ma Kun Zhang Ai-Yu Zhou Yu Zhang Huaqian Wang Zhiyun Du Deng-Gao Zhao

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c16-00030, (Released:2016-03-24)

参考文献数

18

被引用文献数

6 14

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Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against NO overproduction in LPS-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol–ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of TNF-α and IL-1β. Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases.