Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
52 巻, 8 号
選択された号の論文の32件中1~32を表示しています
Review
  • Ken-ichi Harada
    2004 年 52 巻 8 号 p. 889-899
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    Freshwater cyanobacteria produce lethal toxins such as microcystins and anatoxins. During the purification of microcystins in bloom samples we found that a toxic cyanobacterium produced not only microcystins but also other types-peptides in early 1990. Since then we have isolated approximately thirty peptides from freshwater cyanobacteria. In this manuscript we focused on the following topics concerning the isolated peptides: 1) how to isolate desired compounds and to determine their structures, 2) structural classification of isolated compounds, 3) isolation of similar peptides from laboratory strains and bloom materials, 4) structurally related peptides from freshwater and marine origins, 5) β-amino acid containing peptides from cyanobacteria, 6) comprehensive analysis system for the biosynthetic study of peptides produced by cyanobacteria, 7) biological activities of isolated compounds.
  • Kaneto Uekama
    2004 年 52 巻 8 号 p. 900-915
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    The pharmaceutically useful cyclodextrins (CyDs) are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in design and evaluation of CyD-based drug formulation, focusing on their ability to enhance the drug absorption across biological barriers, the ability to control the rate and time profiles of drug release, and the ability to deliver a drug to a targeted site.
  • Hiromitsu Takayama
    2004 年 52 巻 8 号 p. 916-928
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.
Regular Articles
  • Naciye Türkel, Melek Berker, Ulviye Özer
    2004 年 52 巻 8 号 p. 929-934
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    The interactions of aluminium(III) ion with the triprotic catechol derivatives (H3L), 2,3-dihydroxybenzoic acid (2,3-DHBA), 3,4-dihydroxyphenylacetic acid (3,4-DHPA), 3,4-dihydroxybenzoic acid (3,4-DHBA), and 3,4-dihydroxyhydrocinnamic acid (3,4-DHHCA) were investigated in aqueous solution at 25.0 °C. The Calvin–Bjerrum titration method was adopted for the determination of formation constants of proton–ligand and aluminium(III)–ligand complexes. Potentiometric and spectroscopic results indicated that these catechol derivatives exhibit a true bidentate character. The chelation occurs via their catecholate sites, with the exception of 2,3-DHBA. In the case of 2,3-DHBA complexes, the dominant species are either the salicylate type (COO, O) or catecholate type (O, O) complex. The protonation constants of ligands and their formation constants of Al(III) complexes were also correlated. The order of decreasing stabilities of complexes is: 3,4-DHPA>3,4-DHBA>3,4-DHHCA>2,3-DHBA.
  • Shunji Aoki, Dexin Kong, Kouhei Matsui, Rachmaniar Rachmat, Motomasa K ...
    2004 年 52 巻 8 号 p. 935-937
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    A new sesquiterpene aminoquinone, 5-epi-smenospongorine, together with nine known sesquiterpene quinone/phenols, was isolated as differentiation-inducing substances to K562 cells into erythroblast from the marine sponge Dactylospongia elegans. The structure–activity relationship study of these compounds clarified that the quinone skeleton is indispensable and the amino group plays an important role for their differentiation-inducing activity to K562 cells into erythroblast.
  • Kotaro Iida, Yukari Inagaki, Hiroaki Todo, Hirokazu Okamoto, Kazumi Da ...
    2004 年 52 巻 8 号 p. 938-942
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    The effects of the surface processing of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate were investigated. Lactose carrier particles were processed using a high-speed elliptical-rotor-type powder mixer (Theta-Composer®). In the present study, drug/carrier powder mixtures were prepared, consisting of micronized salbutamol sulfate and coarse lactose carriers with various particle surface conditions prepared by surface processing. These powder mixtures were aerosolized by a Jethaler®, and the in vitro inhalation properties of salbutamol sulfate were evaluated with a twin impinger. Compared with those of the powder mixed with unprocessed lactose carriers, the in vitro inhalation properties of the powder mixture prepared using the surface processed lactose carriers were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. The in vitro inhalation properties increased with the rotor rotation rate. Using this surface processing system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.
  • Toshihiko Ishizaka, Yohko Miyanaga, Junji Mukai, Kiyokazu Asaka, Yuka ...
    2004 年 52 巻 8 号 p. 943-948
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    The purpose of this study was to evaluate the bitterness of 18 different antibiotic and antiviral drug formulations, widely used to treat infectious diseases in children and infants, in human gustatory sensation tests and using an artificial taste sensor. Seven of the formulations were found to have a bitterness intensity exceeding 1.0 in gustatory sensation tests (evaluated against quinine as a standard) and were therefore assumed to have an unpleasant taste to children. The bitterness intensity scores of the medicines were examined using suspensions in water or an acidic sports drink. In the case of three macrolide antibiotic formulations containing erythromycin (ERYTHROCIN® dry syrup), clarithromycin (CLARITH® dry syrup for pediatric), and azithromycin (ZITHROMAC® fine granules for pediatric use), the bitterness intensities of suspensions in acidic sports drinks were dramatically enhanced compared with the corresponding scores of suspensions in water. This enhancement could be predicted using the taste sensor. On the other hand, a reduction of bitterness intensity was observed for an acidic sports drink suspension of an amantadine product (SYMMETREL® fine granules) compared with an aqueous suspension. This reduction in bitterness could also be predicted using the taste sensor output value. Thus, the taste sensor could predict whether or not suspension in an acidic sports drink would enhance or reduce the bitterness intensity of pediatric drug formulations, compared with suspensions in water.
  • Fumihiro Nagashima, Moyoko Murakami, Shigeru Takaoka, Yoshinori Asakaw ...
    2004 年 52 巻 8 号 p. 949-952
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    A new aromadendrane-type sesquiterpenoid, 4(15)-aromadendren-12,5α-olide and an aromadendrane–guaianolide dimer have been isolated from the New Zealand liverwort Chiloscyphus subporosus. Their structures were established by extensive NMR techniques and X-ray crystallographic analysis.
  • Hitoshi Kagawa, Tetsuya Takahashi, Mariko Uno, Shigeru Ohta, Yoshihiro ...
    2004 年 52 巻 8 号 p. 953-956
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    Deuterium incorporation at the C-3 position of flavanones was achieved by treatment of flavanones and 2′-hydroxychalcones with D3PO4 and AcOD. We propose that the deuteration reaction mechanism for 2′-hydroxychalcones substrates is as follows. In the first step, 2′-hydroxychalcones cyclize to the corresponding flavanones by an intramolecular Michael-type reaction. Then deuteriums are incorporated into the flavanones via enolization.
  • Beom Soo Shin, Ji Hoon Jung, Kang Choon Lee, Sun Dong Yoo
    2004 年 52 巻 8 号 p. 957-960
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    This study was performed to examine the absorption potential of polyethylene glycol (PEG)-modified salmon calcitonin (sCT) in rats administered via the nasal route. Previous studies have used relatively high molecular weight polyethylene glycols (e.g., ≥5000 daltons) for PEG-modification of sCT to provide increased metabolic stability and biological half-life. Unlike these studies, the present study utilized a low molecular weight succinimidyl-propionated monomethoxy-poly(ethylene glycol) (MW 2000). It was hypothesized that the potential for membrane transport would not be significantly altered due to a relatively small increase in the molecular size while the metabolic stability would be enhanced due to resistance to proteolytic degradation. After PEG-modification of sCT, the mono-PEG positional isomer (mono-PEG2k-sCT) was separated from di-PEG2k-sCT, tri-PEG2k-sCT, and unmodified sCT by size exclusion chromatography. The mono-PEG2k-sCT and unmodified sCT were radioiodinated, and the resulting 125I-sCT and 125I-mono-PEG2k-sCT were separated from free iodine by RP HPLC and confirmed by MALDI-TOF MS. The 125I-sCT and 125I-mono-PEG2k-sCT were administered to rats via the nasal route, and serial blood, tissue, and urine samples were taken for up to 36 h for the determination of radioactivity. Mono-PEG2k-sCT exhibited significantly increased AUC (20638 vs. 3650 ng·min/ml), tmax (520 vs. 77 min), and t1/2,λz (923 vs. 199 min) compared with unmodified sCT. This study demonstrates that mono-PEG2k-sCT is absorbed systemically when given by the intranasal route, exhibiting altered absorption kinetics compared with unmodified sCT.
  • Toshiro Fukami, Atsushi Mugishima, Toyofumi Suzuki, Shinji Hidaka, Tom ...
    2004 年 52 巻 8 号 p. 961-964
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    Improvement of solubility for fullerene (C60) was studied by cogrinding with cycloamyloses using a ball mill in the solid state. Cycloamylose is a novel cyclic α-1,4-glucan produced from synthetic amylose by enzymatic reaction. Although sample solutions showed a pale yellow for the initial period of cogrinding with cycloamyloses and C60, the color varied to brown after 48 h. Subsequently, the solubility of C60 was improved markedly to 560 (μg/ml) at 96 h. From powder X-ray diffraction analysis, the peak intensity of crystalline C60 decreased as the cogrinding time was extended. The UV–VIS absorption spectrum of C60 shows absorption bands at 262 and 340 nm in water with cycloamyloses, and 258 and 328 nm in n-hexane. These results suggested that C60 molecules were dispersed into cycloamyloses micellar system and the red-shift of the UV–VIS spectra was due to an intermolecular interaction between C60 and cycloamyloses.
  • Martin Chwalek, Karen Plé, Laurence Voutquenne-Nazabadioko
    2004 年 52 巻 8 号 p. 965-971
    発行日: 2004年
    公開日: 2004/08/10
    ジャーナル フリー
    Glycosylation of hederagenin with the trichloroacetimidate derivatives of six commercial disaccharides (D-cellobiose, D-lactose, D-maltose, D-melibiose, D-gentiobiose, D-isomaltose) was performed giving the protected saponins in high yields. Deprotection then gave the saponins which were transformed into the corresponding methyl esters. The hemolytic activity of these synthetic hederagenin diglycosides was measured in order to establish structure–activity relationships based on the type and sequence of the attached sugar for the free carboxylic acid and methyl ester saponins.
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