Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 33, Issue 9
Displaying 1-50 of 91 articles from this issue
  • YASUSHI ITOI, MASAMI INOUE, SABURO ENOMOTO
    1985 Volume 33 Issue 9 Pages 3583-3588
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The epoxidation of C5 to C8 olefins with hydrogen peroxide (30%) was studied on molybdenum oxide-Bu3SnCl-charcoal in isopropyl alcohol at 50°C. The yields were remarkably increased by using chemically pretreated charcoals as supports. As modifiers of charcoal, butylating or trimethylsilylating agents gave good results. Cycloolefins of C5 to C8 and an inner olefin, 2-octene, selectively gave epoxides in 90 to 70% yields compared with yields of 60 to 40% on the catalyst prepared from raw charcoal. The increase in yield was attributed to the prevention of the decomposition of hydrogen peroxide.
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  • SABURO SHIMABAYASHI, MASAYUKI NAKAGAKI
    1985 Volume 33 Issue 9 Pages 3589-3594
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The properties of calcium phosphate (CaPi) formed in supersaturated solution (prepared by mixing CaCl2 and K2HPO4 at neutral pH) were studied by means of a Coulter counter and a calcium ion-specific electrode. It was found that the mean particle diameter (φ) of CaPi formed initially increased and then levelled off with time. The rate of increase of φ, however, decreased with increase in the amount of sodium chondroitin-6-sulfate (Na2Chs) added to the mother solution, presumably because of the dispersing effect of Na2Chs. The number concentration of formed particles of CaPi increased at first but after a short period it decreased with time because of the formation and aggregation of secondary particles. Remarkable consumption of Ca2+ was observed at two points in the time course of the precipitation reaction : (1) immediately after mixing the reactants, and (2) after and induction period (ttrans required for the crystallization of amorphous CaPi as hydroxyapatite (HAP), as was confirmed by measurement of the X-ray powder diffraction pattern. The lag time, ttrans, was not affected by the amount of Na2Chs added, but decreased with increase in the amount of CaPi precipitated or of seed HAP inoculated. The physiological significance of the present work is briefly discussed.
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  • TOMOHARU SANO, HIDEO INOUE, TOHRU UEDA
    1985 Volume 33 Issue 9 Pages 3595-3598
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    2'-Deoxy-6, 2'-methano-cyclouridine, a carbon-bridged cyclonucleoside fixed in a high-anti conformation, was synthesized. Treatment of a 3', 5'-O-protected 6-cyano-2'-O-imidazolythiocarbonyluridine with tri-n-butyltin hydride afforded a 6, 2'-oxomethano-cyclouridine derivative in low yield. Base treatment of 5-bromo-2'-deoxy-2' (S)-ethoxycarbonylmethyl-3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) uridine resulted in an intramolecular Michael reaction followed by dehydrobromination to give the 6, 2'-cyclonucleoside. The latter was de-ethoxycarbonylated by treatment with sodium chloride and water in dimethylsulfoxide followed by desilylation to furnish the title compound.
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  • TETSUYA TAKEYA, TORU OKUBO, SHOICHI NISHIDA, SEISHO TOBINAGA
    1985 Volume 33 Issue 9 Pages 3599-3607
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Several (±)-dibenzocyclooctadiene lignans, (±)-deoxyschizandrin (2a), (±)-wuweizisu C (2b), and their stereoisomers 3a, 3b, and 3b-TBC, were synthesized stereospecifically from corresponding phenylacetones 5a and 5b in four steps.
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  • YOSHIRO KOBAYASHI, TSUTOMU YOSHIDA, MASAHARU NAKAJIMA, AKIRA ANDO, YUJ ...
    1985 Volume 33 Issue 9 Pages 3608-3616
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The thermolysis of 1, 5, 6, 7-tetrakis (trifluoromethyl)-2, 3, 4-triazabicyclo [3.2.0] hepta-2, 6-diene (3) without a solvent gave 1-[1, 2, 3-tris (trifluoromethyl) cyclopropenyl]-2, 2, 2-trifluoroethylimine (2). The flash vacuum pyrolysis of 3 gave 1, 2, 3-tris (trifluoromethyl) cyclopropene (6). 1, 2, 3, 4-Tetrakis (trifluoromethyl) pyrrole (5) was produced in both reactions. 1, 2, 3-Tris (trifluoromethyl) cyclopropen-3-yl trifluoromethyl ketone (1) and 2 were found to react as good dienophiles and gave products obtained through the transition states where the electron-deficient part of the dienophiles attracted the electron-rich part of the diene components, a hetero atom or the diene moiety.
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  • TOMOHARU SANO, SATOSHI SHUTO, HIDEO INOUE, TOHRU UEDA
    1985 Volume 33 Issue 9 Pages 3617-3622
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The reaction of methylenetriphenylphosphorane with 2'-keto-3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) uridine afforded the 2'-methyleneuridine (1). Oxidation of 1 with osmium tetroxide and tert-butyl hydroperoxide or N-methylmorpholine-N-oxide afforded a mixture of a 2'-hydroxymethyluridine (2) and its arabinosyl isomer. Oxidation at lower temperature gave the former as the main product. Compound 2 was converted to the 5-bromo-2'-iodomethyl derivative (3) through the 2'-mesyloxy compound, and 3 was treated with tri-n-butyltin hydride to give the 6, 2'-methano-cyclo-5, 6-dihydro derivative (4). Compound 4 was dehydrobrominated and deprotected to furnish 6, 2'-methano-cyclouridine, a uridine fixed in high-anti conformation. Some results on the synthesis and cleavage of the 2'-spiro-epoxy derivative prepared from the 2'-ketouridine are also presented.
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  • SEIICHI MATSUGO, MITSUO SAITO, AKIRA TAKAMIZAWA
    1985 Volume 33 Issue 9 Pages 3623-3634
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The reaction of 2-aryl-5-phenyl-2, 4-dihydro-3H-pyrazol-3-ones (1) with cyclopentanone (5a) in the absence of NEt3 gives 2-aryl-4-cyclopentylidene-5-phenyl-2, 4-dihydro-3H-pyrazol-3-ones (7) in nearly quantitative yield. In the presence of NEt3, the reaction of 1 with 5a gives 2-aryl-4-cyclopentyl-5-phenyl-2, 4-dihydro-3H-pyrazol-3-ones (6a-c) in ca. 40% yields together with epoxides (8a-c). Similarly, various 4-cycloalkyl-2-aryl-5-phenyl-2, 4-dihydro-3H-pyrazol-3-ones (6d-i) were obtained in ca. 40% yields. In these reactions, the expected cycloalkylidene products were reduced to cycloalkyl derivatives. The reaction mechanisms and the synthetic utility of these reactions are discussed.
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  • TOZO FUJII, TOHRU SAITO
    1985 Volume 33 Issue 9 Pages 3635-3644
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The reaction rates in the Dimroth rearrangements of 9-substituted 1-methyladenines (5a-i) were measured in H2O at various pH's and ionic strength 1.0 at 40°C. In all cases, attack of hydroxide ion on the protonated species of 5 at the 2-position was faster than that on the neutral species by a factor of 90-180. Among nine kinds of 9-substituents in these compounds, the β-D-ribofuranosyl group was found to accelerate both modes of hydroxide attack most significantly. It has been concluded that this rate enhancement is attributable solely to the electron-withdrawing effect of the furanose ring oxygen and not to the 5'-hydroxy group, a potential participant in intramolecular catalysis for the hydroxide attack on the adenine ring at the 2-position.
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  • HIROMI KOBAYASHI, HIROKO KARASAWA, TOSHIO MIYASE, SEIGO FUKUSHIMA
    1985 Volume 33 Issue 9 Pages 3645-3650
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Seven iridoid glycosides (I-VII) have been isolated from Cistanchis Herba, the whole plant of Cistanche salsa (C. A. MEY.) G. BECK (Orobanchaceae). The structure of a new compound, 6-deoxycatalpol (V), and the identity of the other glycosides have been established by chemical transformations and spectral analyses of the compounds and their derivatives. Mussaenosidic acid (I) was isolated for the first time as a natural product.
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  • TAKESHI DEYAMA, TAKAKO IKAWA, SANSEI NISHIBE
    1985 Volume 33 Issue 9 Pages 3651-3657
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Three new lignan glycosides were isolated from the bark of Eucommia ulmoides OLIV. (Eucommiaceae). Their structures were established as (-)-olivil 4', 4"-di-O-β-D-glucopyranoside (1), (+)-1-hydroxypinoresinol 4', 4"-di-O-β-D-glucopyranoside (2) and (+)-medioresinol 4'-O-β-D-glucopyranoside (named eucommin A) (3), based on chemical evidence and spectroscopic studies. A known lignan glycoside, (+)-syringaresinol O-β-D-glucopyranoside (4) was also isolated.
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  • KOJI WADA, HIDEO BANDO, TAKAO MORI, RIHO WADA, YOSHIO KANAIWA, TAKASHI ...
    1985 Volume 33 Issue 9 Pages 3658-3661
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    A new alkaloid, 14-benzoylneoline, and four known alkaloids, neoline, karakoline, 14-acetyldelcosine, and penduline, were isolated from the roots of Aconitum subcuneatum NAKAI. The structures of 14-benzoylneoline and penduline were confirmed by derivation of these compounds from neoline and aconitine, respectively. A radical-type deoxygenation of a bridgehead hydroxyl group at C-13 was used in the transformation of aconitine into penduline through three steps.
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  • FUMIKO ABE, TATSUO YAMAUCHI
    1985 Volume 33 Issue 9 Pages 3662-3669
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Affinosides La-Le, major cardenolide glycosides which have oxygen functions at C-11 and C-12 or at C-11 of the aglycone moiety, and retain double linkages between the 2α, 3β-dihydroxyl groups of the aglycone and 6-deoxy-, or 6-deoxy-3-O-methylgulosulose, were isolated from the leaves of Anodendron affine, and the structures were determined on the basis of spectral and chemical evidence.
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  • KOSUKE KAWADA, OSAMU KITAGAWA, YOSHIRO KOBAYASHI
    1985 Volume 33 Issue 9 Pages 3670-3674
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    3-Trifluoromethylfuran (1) was efficiently synthesized by the reaction of 4-methyloxazole with 3, 3, 3-trifluoropropyne. Lithiation of 1 with n-butyllithium followed by reaction with an electrophile gave the corresponding 2-substituted 3-trifluoromethylfuran (4). Starting from 2-triethylsilyl-3-trifluoromethylfuran (4a), 2-substituted 4-trifluoromethylfurans (6) were synthesized.
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  • MASAMI KATO, TADAHIRO TAKEDA, YUKIO OGIHARA, MASAKI SHIMIZU, TAKEO NOM ...
    1985 Volume 33 Issue 9 Pages 3675-3680
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Water-soluble polysaccharides were isolated from Tetragonia tetragonoides (Aizoaceae), and their anti-inflammatory effects on carrageenan-induced edema and adjuvant arthritis were tested. One of the active fractions TIIc, gave a single peak on high-performance liquid chromatography and gel filtration. Methylation, periodate oxidation and carbon-13 nuclear magnetic reasonance spectroscopic studies suggested that TIIc is composed of the following repeating unit : [numerical formula]
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  • MIKIO HORI, TADASHI KATAOKA, HIROSHI SHIMIZU, EIJI IMAI, YUKIHARU MATS ...
    1985 Volume 33 Issue 9 Pages 3681-3688
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Reactions of 7-substituted 1, 3, 9-trimethyl-8, 9-dihydroxanthines (3) with dimethyl acetylenedicarboxylate afforded heteropropellanes (5) in good yields. The reactions with methyl propiolate afforded pyrimidodiazepines (7) as well as propellanes (6) when the xanthines have small substituents at the 7 position. The mechanisms of formation of the products are also discussed.
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  • TOHRU UEDA, SHINICHI WATANABE
    1985 Volume 33 Issue 9 Pages 3689-3695
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Condensation of 3, 4, 6-tri-O-acetyl-D-glucal and trimethylsilylated nucleobases in the presence of stannic chloride or trimethylsilyl trifluoromethanesulfonate gave anomeric mixtures of 2, 3-dideoxy-D-erythro-hex-2-enopyranosyl nucleosides. The signs of the circular dichroism (CD) spectra of the anomeric 2-hexenopyranosyl nucleosides are opposite to those of usual nucleosides or glucopyranosyl nucleosides. Other examples illustrating the contribution of an unsaturated bond in the sugar portion of nucleosides to the CD spectra are also presented.
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  • MASANORI SOMEI, KIYOMI KIZU, MASAKO KUNIMOTO, FUMIO YAMADA
    1985 Volume 33 Issue 9 Pages 3696-3708
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Various 4-halogeno-3-indoleacetic acids and -3-indoleacetonitriles were synthesized for the first time by means of the Sandmeyer or Schiemann reaction, demonstrating the versatility of 4-indolediazonium salts in 4-substituted indole chemistry. A practical synthetic method for 4-halogenoindoles was developed by regio-selective thallation-halogenation, and the products were also led to 4-halogeno-3-indoleacetic acids. The first synthesis of 4-formyl-3-indoleacetonitrile is also reported.
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  • KATSUHIDE MATOBA, FUJIKO KAWAGOSHI, MINAKO TANABE, TAKAO YAMAZAKI
    1985 Volume 33 Issue 9 Pages 3709-3714
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    2-Methoxy-4, 4-diphenyl-2, 5-cyclohexadienone (Ib) was irradiated with a 100 W mercury lamp in methanol to give methyl 5-methoxy-6, 6-diphenyl-2, 5-hexadienoate (II) or its oxidized product, 9-(4-carbomethoxy-1-methoxy-2-butenylidene)-9H-fluorene (IV), and in benzene to give 6-methoxy-5, 6-diphenyl-2, 4-cyclohexadienone (VI) and 1-methoxy-6, 6-diphenylbicyclo [3.1.0] hex-3-en-2-one (VII). 2-Methoxy-4, 4-diphenyl-2-cyclohexenone (XIa) was irradiated in benzene or methanol to give 1-methoxy-5, 6-diphenylbicyclo [3.1.0] hexan-2-one (XII) in good yield. Finally, 4-dichloromethyl-2-methoxy-4-methyl-2, 5-cyclohexadienone (Ic) in methanol gave 6-dichloromethyl-2, 2-dimethoxy-6-methylbicyclo [3.1.0] hexan-3-one (XIV) and 5-dichloromethyl-6, 6-dimethoxy-5-methyl-2-cyclohexenone (XV).
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  • ERIKO AKAI, TADAHIRO TAKEDA, YOSHIMASA KOBAYASHI, YUKIO OGIHARA
    1985 Volume 33 Issue 9 Pages 3715-3723
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Three sulfated tetraglycosides of oleane-type triterpenoids, rotundiosides A (1), B (2) and C (3), isolated from the leaves of Bupleurum rotundifolium L., were characterized as the 3β-sulfate ester of 16α-hydroxyolean-12-ene-28-oyl β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl (1→2)-β-D-glucopyranosyl (1→6)-β-D-glucopyranoside, the 3β-sulfate ester of olean-12-ene-28-oyl β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl (1→6)-β-D-glucopyranoside and the 3β-sulfate ester of olean-12-ene-28-oyl β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl (1→2)-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside, respectively, on the basis of chemical and spectroscopic evidence.
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  • MASASHI OHBA, MITSUKO HAYASHI, TOZO FUJII
    1985 Volume 33 Issue 9 Pages 3724-3730
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The first total synthesis of the Alangium vitiense alkaloid 9-demethyltubulosine (1) has been achieved in the form of a racemic modification through a"lactim ether route, " which included the intermediates (±)-7, (±)-8, (±)-10, and (±)-9. The 1'α-Hisomers (±)-12 and (±)-11 were also produced through this synthetic route. On the other hand, the nonconformity of synthetic (±)-1 with another (-)-demethyltubulosine from A. lamarckii indicated the alternative 10-demethyl structure (2) to be correct for the A. lamarckii alkaloid. The assignments of the configuration at C-1' of (±)-1, (±)-9, (±)-11, and (±)-12 were based on four criteria, namely, the ratio of products from the catalytic reduction of (±)-10, thin-layer chromatographic mobility, and 1H and 13C nuclear magnetic resonance spectral features.
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  • NOBUTAKA FUJII, SHIROH FUTAKI, KENICHI AKAJI, HARUAKI YAJIMA, ATSUKO I ...
    1985 Volume 33 Issue 9 Pages 3731-3737
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Two Trp containing peptides, neuromedins B and C, were synthesized using a new Trp derivative, Nin-mesitylenesulfonyltryptophan, [Trp (Mts)]. The thioanisole-mediated deprotection with trifluoromethanesulfonic acid in trifluoroacetic acid was employed at the final steps of these syntheses to remove the Mts group together with the Nα-protecting group. In this deprotecting step, the use of an additional scavenger, ethanedithiol, was recommended to suppress possible indole modification. When smooth-muscle contractile activity in guinea pig ileum was examined, the relative potencies of neuromedins B and C with respect to synthetic substance P (taken as 1) were 0.46 and 0.37, respectively.
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  • HISAO KAKEGAWA, NAOKI MITSUO, HITOSHI MATSUMOTO, TOSHIO SATOH, MASAAKI ...
    1985 Volume 33 Issue 9 Pages 3738-3744
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    We found that N-(trans-3, 4-dimethoxycinnamoyl) anthranilic acid (tranilast) is readily transformed by photo-irradiation to N-(cis-3, 4-dimethoxycinnamoyl) anthranilic acid (cis-isomer) and a cyclobutane derivative (dimer). Of these photo-irradiated products of tranilast, the cis-isomer was found to inhibit hyaluronidase more effectively than tranilast. From these results, it wsa expected that the cis-isomer might have more effective anti-allergic activity than tranilast ; indeed, the cis-isomer was found to show more effective prevention than tranilast of (1) histamine release from sensitized rat peritoneal mast cells induced by antigen (egg white albumin), (2) histamine release from rat peritoneal mast cells induced by concanavalin A and calcium ionophore A-23187, and (3) the 48 h homologous passive cutaneous anaphylaxis (PCA) in rats.
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  • KAYOKO OKAMOTO, MUTSUKO MATSUMOTO, MASAZUMI WATANABE, MITSURU KAWADA, ...
    1985 Volume 33 Issue 9 Pages 3745-3755
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    2, 3-Dimethoxy-5-methyl-1, 4-benzoquinones having an ω-hydroxyalkyl or ω-aminoalkyl group at the 6-position were synthesized. The effects of these compounds and related compounds on the respiratory system of ubiquinone-depleted mitochondrial preparations were investigated. The compounds with an alkyl side chain of 10 to 13 carbon atoms showed rather high restoration activity on antimycin-sensitive succinate oxidation in acetone-treated beef heart mitochondria. This activity was correlated with their partition coefficients. Among these compounds, 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (V-10, idebenone) was selected for further testing to determine its effect on the respiratory system of injured canine brain mitochondrial preparation, because this compound showed prominent activity in the system described above. When V-10 was added to acetone-treated canine brain mitochondria (A-CBM), antimycin- and KCN-sensitive succinate oxidation were restored to the level observed in the freeze-stored canine brain mitochondria (CBM). V-10 also restored the reduced nicotinamide adenine dinucleotide (NADH) oxidation of pentane-treated canine brain mitochondria and submitochondrial particles (P-CBM and P-CBSM). Metabolites (I-4, I-10) of V-10 in human and animals showed no restoration activity in either respiratory enzyme system.
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  • KAYOKO OKAMOTO, EIJI MIZUTA, KAZUHIDE KAMIYA, ISUKE IMADA
    1985 Volume 33 Issue 9 Pages 3756-3765
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Sulfate conjugates of ubiquinone metabolites (Ia, Ib) and related compounds including 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, Id-10) were synthesized. Chemical shifts in the proton nuclear magnetic resonance (1H-NMR) spectra of the 1- and 4- sulfates were assigned by investigating differences in the low-field shifts between model compounds and the corresponding sulfates, and by regio-specific synthesis of the 4-sulfates.
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  • TADAO KOJIMA, KUNIHIRO NIIGATA, TAKASHI FUJIKURA, SHIRO TACHIKAWA, YOS ...
    1985 Volume 33 Issue 9 Pages 3766-3774
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The synthesis of (±)-2-[(inden-7-yloxy) methyl] morpholine hydrochloride (7·HCl, YM-08054, indeloxazine hydrochloride) and its optical resolution into levo- and dextro-isomers were investigated. A practical synthetic method for 7·HCl was established by employing preferential crystallization from an equilibrium mixture of 7·HCl and its tautomer, (±)-2-[(inden-4-yloxy)-methyl] morpholine hydrochloride (6·HCl), in the presence of a catalytic amount of base in MeOH. It was found that 7·HCl and its levo-rotatory isomer ((-)-7·HCl) showed not only strong antidepressive activities, but also potent cerebral-activating properties. The syntheses and pharmacological activities of related compounds are also discussed briefly.
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  • MINORU UCHIDA, FUJIO TABUSA, MAKOTO KOMATSU, SEIJI MORITA, TOSHIMI KAN ...
    1985 Volume 33 Issue 9 Pages 3775-3786
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    A series of N-acyl amino acid analogues of 2 (1H)-quinolinone was synthesized and tested for antiulcer activity against acetic acid-induced gastric ulcer in rats. These compounds were synthesized by the acylation of amino acid derivatives of 2 (1H)-quinolinone, which were obtained from the reaction of ω-bromoalkyl 2 (1H)-quinolinones and acetamidomalonate in the presence of sodium ethoxide, followed by hydrolysis with diluted hydrochloric acid. Among them, 2-(4-chlorobenzoylamino)-3-[2 (1H)-quinolinon-4-yl] propionic acid (VIIIf) was found to have the most potent activity. The structure-activity relationships are discussed.
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  • KANJI MEGURO, MASAHIRO AIZAWA, TAKASHI SOHDA, YUTAKA KAWAMATSU, AKINOB ...
    1985 Volume 33 Issue 9 Pages 3787-3797
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    In a search for new 1, 4-dihydropyridine derivatives with a long-lasting effect on the cardiovascular system, a series of piperazinylalkyl esters (I) bearing a lipophilic substituent on the 4-nitrogen of the piperazine ring was synthesized and tested for hypotensive effect in spontaneously hypertensive rats (SHR). Compounds I, especially those having a diphenylmethyl moiety on the piperazine ring, showed extremely potent and long-lasting hypotensive properties. Analogues related to I were also prepared, and the structure-activity relationships are discussed.
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  • MICHIYUKI SENDAI, SHOHEI HASHIGUCHI, MITSUMI TOMIMOTO, SHOJI KISHIMOTO ...
    1985 Volume 33 Issue 9 Pages 3798-3810
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    In the course of the chemical modification of sulfazecin, several 4-carbamoyl-2-azetidinone-1-sulfonic acid derivatives were synthesized with the aim of improving the antibacterial activity. Among those compounds, (3S, 4S)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-(1-carboxy-1-methylethoxyimino) acetamido]-4-carbamoyl-2-azetidinone-1-sulfonic acid (2) was found to have potent antibacterial activity, comparable to that of carumonam (1, AMA-1080 ; Ro 17-2301), against gramnegative bacteria. Efficient synthetic pathways to prepare 1 and 2 in large quantities were developed based on (2R, 3R)-epoxysuccinic acid (5), an easily accessible fermentation product, as a starting chiral synthon.
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  • MITSUGU KOBAYASHI, HIROSHI NOGUCHI, USHIO SANKAWA
    1985 Volume 33 Issue 9 Pages 3811-3816
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Formononetin (1), isoliquiritigenin (2), echinatin (3), liquiritigenin (4), p-hydroxybenzoic acid (5), 3'-hydroxyformononetin (6) and isobavachalcone (7) were isolated from callus culture of Glycyrrhiza uralensis which was established on Murashige-Skoog's medium containing naphthaleneacetic acid (NAA, 2ppm), (2, 4-dichlorophenoxy) acetic acid (2, 4-D, 1ppm) and benzyladenine (0.1ppm). Formononetin (1), 3'-hydroxyformononetin (6) and isobavachalcone (7) showed different patterns of production.
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  • ISAO KUBO, AKIKO MATSUMOTO
    1985 Volume 33 Issue 9 Pages 3817-3820
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    A bitter insect-antifeedant dihydrochalcone, phloretin 4'-O-β-D-glucopyranoside, was isolated from fresh apple leaves by using rotation locular counter-current chromatography (RLCC), and the preferred conformation in solution was determined by means of proton (1H-) and carbon-13 (13C-) nuclear magnetic resonance (NMR) experiments.
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  • ISAO KUBO, AKIKO MATSUMOTO, MUTSUO KOZUKA, WILLIAM F. WOOD
    1985 Volume 33 Issue 9 Pages 3821-3825
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Calmodulin inhibitors were found in the bitter poisonous mushroom Naematoloma fasciculare (Fr.) KARST. (Strophariaceae). The active compounds, fasciculols B, C, and F, were isolated by droplet counter-current chromatography and identified on the basis of various physical and spectral data. Application of the dibenzoate chirality method to a p-bromobenzoate derivative of fasciculol C allowed the absolute configurations at the C-2 and C-3 positions to be determined as (R) and (S), respectively.
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  • ISAO KUBO, AKIKO MATSUMOTO, MAKOTO TANIGUCHI, WILLIAM F. WOOD
    1985 Volume 33 Issue 9 Pages 3826-3828
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Hydroquinone and (-)-epicatechin were isolated from seeds of Aesculus californica NUTT. (Hippocastanaceae), and their effect on the growth of lettuce and rice seedlings was examined. Hydroquinone inhibited germination at high concentrations (above 100μg/ml) but it stimulated growth at low concentrations for both lettuce and rice seedlings. (-)-Epicatechin showed little activity by itself. However, when applied with hydroquinone, (-)-epicatechin tended to counteract the growth inhibitory activity of hydroquinone.
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  • TADATO TANI, TADAHISA KATSUKI, MICHINORI KUBO, SHIGERU ARICHI, ISAO KI ...
    1985 Volume 33 Issue 9 Pages 3829-3833
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    In order to clarify the distribution of soyasaponins, which are the bioactive constituents of the seeds of Glycine max MERRILL, in various organs of soybeans, histochemical analysis has been performed. By means of high-performance liquid chromatography of fluorescent derivatives of the saponins, it was found that soyasaponins, except soyasaponin II, are located predominantly in certain organs of soybeans (the plumule, hypocotyl, and radicle) which subsequently grow to form the adult plant.
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  • TADATO TANI, TADAHISA KATSUKI, MICHINORI KUBO, SHIGERU ARICHI, ISAO KI ...
    1985 Volume 33 Issue 9 Pages 3834-3837
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The possible relationship between some morphological characteristics of soybeans and the contents of their bioactive components (tocopherols and isoflavones) was histochemically examined. It was found that tocopherols were distributed at high concentration in the cotyledon and that isoflavones were mainly localized in the plumule, hypocotyl, and radicle, which subsequently grow to form the adult plant. It was also found that the isoflavone content in soybeans with greencolored seed coats might be higher than that in soybeans with yellow seed coats.
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  • MASAO HATTORI, YUEZHONG SHU, MINEO SHIMIZU, TOSHIMITSU HAYASHI, NAOKAT ...
    1985 Volume 33 Issue 9 Pages 3838-3846
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    In the course of studies on the metabolism of active components of crude drugs by intestinal bacteria, paeoniflorin, oxypaeoniflorin, and benzoylpaeoniflorin isolated from the roots of Paeonia albiflora PALLAS (Paeoniaceae) were incubated with a human fecal suspension. Paeoniflorin, as well as oxypaeoniflorin and benzoylpaeoniflorin, was converted to three metabolites (paeonimetabolines I, II and III) by intestinal bacteria. The structure of the major metabolite (paeonimetaboline I) was elucidated by spectroscopic methods. Through screening of various strains of intestinal bacteria from human feces, Peptostreptococcus anaerobius was shown to have potent ability to transform paeoniflorin to paeonimetaboline I.
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  • TAICHI OHMOTO, KAZUO KOIKE
    1985 Volume 33 Issue 9 Pages 3847-3851
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Two new alkaloids, picrasidines M (II) and P (III), have been isolated from the root-bark of Picrasma quassioides BENNET. The structure of picrasidine L has been revised from 3-methyl-canthin-2, 6-dione to 3-methylcanthin-5, 6-dione (I). The structures were determined on the basis of spectral analysis and chemical evidence.
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  • TOSHINOBU MORITA, OSAMU TANAKA, HIROSHI KOHDA
    1985 Volume 33 Issue 9 Pages 3852-3858
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    It was found that dammarane-saponin composition of rhizomes of Panax japonicus C. A. MEYER collected in Miyazaki-ken, Kyushu (South-West Province of Japan) was remarkably different from that of specimens (Japanese name : Chikusetsu-ninjin) collected at other places in Japan. From rhizomes of this specimen (local name : "Satsuma-ninjin"), four biologically active major dammarane-saponins of Ginseng roots, ginsenosides-Rg1 (11), -Re (12), -Rc (16) and -Rb1 (17) and two dammarane-saponins of Sanchi-Ginseng, notoginsenosides-R1 (13) and -R2 (9) as well as gypenoside-XVII (14) were isolated together with the saponins of oleanolic acid (1), chikusetsusaponins-IV (3) and -V (5), both of which have already been isolated from Chikusetsuninjin. From Chikusetsu-ninjin, none of 9, 11, 12, 13, 14, 16 and 17 has been isolated, while in "Satsuma-ninjin, "chikusetsusaponins-Ia (6), -III (7), which are the characteristic dammaranesaponins of Chikusetsu-ninjin, were not identified. The present isolation of the major dammarane-saponins of Ginseng roots from "Satsumaninjin"in relatively high yields is significant not only from the viewpoint of the geographical relation of Japanese P. japonicus with Chinese and Himalayan Panax spp. but also from the viewpoint of the pharmacological importance of this specimen in oriental traditional medicine.
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  • TOSHIKAZU SUZUKI, YOSHIMASA HASHIMURA, SHIGEYUKI TAKEYAMA
    1985 Volume 33 Issue 9 Pages 3859-3867
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Chemical oxidation of the positive inotropic agent denopamine, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3, 4-dimethoxyphenethyl) amino] ethanol, and its derivatives by Udenfriend's model system for enzymatic oxidation was studied. The oxidation products were separated and identified by gas chromatography-mass spectrometry and high-performance liquid chromatography. All the metabolites of denopamine produced by enzymatic oxidation were also formed in Udenfriend's system. However, compared to enzymatic oxidation, the chemical oxidation was less selective as to the position of demethylation : i.e., although enzymatic 4'-O-demethylation took place overwhelmingly in preference to 3'-O-demethylation, comparable amounts of the two demethylated isomers were produced in Udenfriend's system. It was also found that the chemical oxidation was more powerful than the enzymatic oxidation because hydroxylation at the ortho or para position to the methoxy group took place in all the substrates tested, while such metabolites have not been detected in biological systems. As in the enzymatic system, tetrahydroisoquinoline-type compounds were formed from substrates in which the hydroxy group was attached at the meta position of the benzene ring. This is presumably a result of Pictet-Spengler-type condensation with formaldehyde generated in the reaction mixture.
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  • HIDEAKI ICHIBA, MUNEO MORISHITA, TAKEHIKO YAJIMA, YASUHITO KAWATSU, MI ...
    1985 Volume 33 Issue 9 Pages 3868-3874
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A normal-phase high performance liquid chromatographic determination of adriamycin and its metabolites, adriamycinol and adriamycinone, in human body fluids (plasma, urine and pleural fluids) is described. Samples were collected from lung cancer patients who had received adriamycin by peripheral vein infusion, bronchial arterial infusion and intrapleural infusion. Adriamycin and its metabolites were easily and efficiently extracted from each biological fluid by the use of an Extrelut[○!R] column. High performance liquid chromatographic separation was carried out in the presence of Mg2+ and the limits of determination of adriamycin, adriamycinone and adriamycinol were found to be 0.52, 0.72 and 0.48ng/ml, respectively. Chromatographic analyses were completed within 8min. The present method was also applied to pharmacokinetic studies of adriamycin, and it was found that the metabolic fate of adriamycin can be well explained by a two-compartment model.
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  • HIROYUKI WAKABAYASHI, KENJI SHIMADA, YOSHIO AIZAWA
    1985 Volume 33 Issue 9 Pages 3875-3880
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    High-performance liquid chromatography (HPLC) of serotonin and melatonin was carried out on a reversed-phase column ; the compounds were determined by fluorescence measurement with excitation and emission wavelengths of 285 and 345nm, respectively. The indoles were clearly separated and eluted with a single mobile phase within 20min. 4-Aminoantipyrine was used as an internal standard (detected by ultraviolet (UV) absorbance measurement). Satisfactory recovery of serotonin and melatonin was obtained by using this dual detection system (UV and fluorescence). The detection limits of the indoles were all in the low picogram range. The proposed method was applied to the determination of serotonin and melatonin in rat pineal gland. A distinct variation between light and dark periods was found in both serotonin and melatonin levels in the rat pineal gland.
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  • YOSHINORI TSUCHIYA, MINEO SHIMIZU, YOSHIYUKI HIYAMA, KIYOSHI ITOH, YOS ...
    1985 Volume 33 Issue 9 Pages 3881-3886
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The antiviral activity of a wide range of naturally occurring flavonoids was investigated in vitro. Chrysosplenol B and chrysosplenol C, which are contained specifically in Chrysosplenium plants, and axillarin showed potent antiviral activity, especially against rhinovirus. A comparison of the activities of the compounds tested indicated that 3-methoxyl and 5-hydroxyl groups in the flavone skeleton were both necessary for antiviral activity against rhinovirus, and the activity may also be affected by various groups at other positions. The other flavonoids tested had little or no antiviral activity against herpes simplex virus, influenza virus and rhinovirus. These results suggest that Chrysosplenium plants, which contain large amounts of chrysosplenol B and chrysosplenol C, may be useful as medicinal herbs against the common cold caused by rhinovirus infection. These plants have not so far been used as a medicinal herb or as a folk medicine, as far as is known.
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  • SUSUMU ISHIMITSU, SADAKI FUJIMOTO, AKIRA OHARA
    1985 Volume 33 Issue 9 Pages 3887-3892
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The hydroxylation of L-phenylalanine was investigated in subcellular fractions of various organs of rat under aerobic conditions. L-Phenylalanine was metabolized to p-, m-, and o-tyrosine in the 2000×g homogenates of liver, kidney, brain and adrenal of male rats. The three metabolites in the incubation mixture were determined by high-performance liquid chromatography. This hydroxylation reaction occurred only in the postmicrosomal fraction of the organs mentioned above but not in the microsomal fractions, and required a pteridine as a cofactor. The hydroxylation of phenylalanine was inhibited by the addition of p-chlorophenylalanine and α-methyltyrosine, which are specific inhibitors of phenylalanine hydroxylase and tyrosine hydroxylase, respectively. On the other hand, superoxide dismutase and potassium iodide, which are known scavengers of the superoxide radical and hydroxyl radical, had no significant effect on the hydroxylation. These results indicate that the hydroxylation of phenylalanine to m- and o-tyrosines is caused mainly by phenylalanine hydroxylase and tyrosine hydroxylase.
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  • TAKAKO YOKOZAWA, TAEKO KOBAYASHI, HIKOKICHI OURA, YUJI KAWASHIMA
    1985 Volume 33 Issue 9 Pages 3893-3898
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The effect of ginsenoside-Rb2 purified from ginseng was investigated in streptozotocin-induced diabetic rats. The rats treated with ginsenoside-Rb2 showed significant decreases in triglyceride, non-esterified fatty acid, and total cholesterol in the serum. A lipid-improving action in the serum was observed in rats with hyperlipemia. Furthermore, the lipolytic activity of lipoprotein lipase was stimulated with a concomitant decrease in the levels of triglyceride and very low density lipoprotein in the serum, while a repressive effect on hormone-sensitive lipase activity was observed. The accumulation of lipid in the adipose tissue was also observed. In addition to the hypolipemic effect, ginsenoside-Rb2 exhibited a lowering action on the serum levels of 3-hydroxybutyrate and acetoacetate in streptozotocin-induced diabetic rats, indicating an improvement of diabetic ketoacidosis.
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  • NAHOKO KANIWA, HIROYASU OGATA, NOBUO AOYAGI, MASANOBU KOIBUCHI, TOSHIO ...
    1985 Volume 33 Issue 9 Pages 3899-3905
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The relationship between the gastric acidity of subjects and the bioavailability of pyridoxal phosphate from commercial enteric-coated tablets having various values of apparent critical pH for dissolution (above which the coated films disintegrate within 3h) was studied. The tablet with an apparent critical dissolution pH of 5.5 appeared not to disintegrate in the stomach even in subjects with anacidity, and the bioavailability was not affected by the gastric acidity of the subjects. However, the bioavailability of the tablet with an apparent critical dissolution pH of 6.6 and a short lag for dissolution at that pH did depend on the gastric acidity of the subjects, and the higher the gastric acidity, the more slowly was the drug absorbed. On the other hand, the enteric-coated tablet with an apparent critical dissolution pH of 4.5 might be subject to disintegration in the stomach of subjects with anacidity.
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  • NAHOKO KANIWA, HIROYASU OGATA, NOBUO AOYAGI, MASANOBU KOIBUCHI, TOSHIO ...
    1985 Volume 33 Issue 9 Pages 3906-3914
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The bioavailability of five enteric-coated tablets and one sugar-coated tablet of pyridoxal phosphate previously tested in humans was studied in beagle dogs, and the dissolution rates of the tablets were measured by various dissolution methods. The results in beagle dogs correlated significantly with those in humans, and beagle dogs can therefore be used as an animal model to predict the bioavailability in humans of enteric-coated tablets of pyridoxal phosphate. On the other hand, dissolution tests were not as useful as the bioavailability test in beagle dogs. Only the dissolution parameter obtained by the oscillating basket method using medium of pH 5.9 correlated significantly with the initial excretion rates of pyridoxic acid found in the human study. The oscillating basket method with pretreatment in the No. 1 medium (J. P. IX) failed to reject tablets having inferior bioavailabilities in humans. Pretreatment with acidic solution in dissolution or disintegration tests was considered to make the prediction of bioavailability less reliable.
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  • MINORU KURODA, TOMOKO KAWATA
    1985 Volume 33 Issue 9 Pages 3915-3921
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Five O/W creams with different hydrophilic-lipophilic balance (HLB) values were prepared. The stability of these creams was examined by means of a storage stability test for three months and a vertical vibrating test which caused a first-order breakdown of viscoelastic structures formed in the creams at the rates of Kη'and KG'were more stable in the storage test. This vibrating test may be useful instead of a prolonged storage test for estimating the stability of creams in comparative screening during development, based on the selection of creams with lower values of Kη'and KG'.
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  • TSUYOSHI GOROMARU, MASATAKA KATASHIMA, HIROSHI MATSUURA, NOZOMU YOSHIM ...
    1985 Volume 33 Issue 9 Pages 3922-3928
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    The metabolites of fentanyl (FT) were identified in isolated rat and guinea pig hepatocytes by gas chromatography-mass spectrum (GC-MS) combined with the stable isotope tracer technique. Isolated hepatocytes were prepared by the collagenase perfusion method and were incubated with a 0.3mM equimolar mixture of FT and FT-d5 citrate in a rotating round-bottomed flask at 37°C. The metabolites were extracted with chloroform. The extracts were subjected to GC and GC-MS after trimethylsilylation. Characteristic doublet peaks in the mass spectra indicated the presence of 6 and 7 metabolites in rat and guinea pig hepatocytes, respectively. 4-(N-Propionylanilino) piperidine was identified as the main metabolite in both species. Other metabolites were oxidation products of the phenethyl, piperidine and propionyl groups of FT. Oxidation of the anilino ring and hydrolysis of the amide bond were not found in hepatocytes.
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  • SHIGEO TANAKA, YASUJI TAKASHIMA, HIROSHI MURAYAMA, SEISHI TSUCHIYA
    1985 Volume 33 Issue 9 Pages 3929-3934
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    Oil-in-water creams having various capacities to dissolve dexamethasone acetate (DA) were prepared by changing the concentration of polysorbate 80. The solubility of DA in the creams and the distribution of DA in each phase of the creams were examined to see how they influenced DA release from the creams. The solubility of DA in the creams was obtained by calculation from the solubility of DA in each component of the cream. These results on DA release were compared with data on the human vasoconstrictor activity of these creams. In creams of low DA concentration, DA was solubilized, and the DA release rate decreased as the concentration of polysorbate 80 increased, being inversely proportional to the solubility of DA in the cream. On the other hand, in creams of high DA concentration, DA was present partially in the soild state, and the DA release rate increased as the concentration of polysorbate 80 increased. The release rate was dependent on the ratio of solubilized DA in the cream. However, vasoconstrictor activity was dependent on the concentration of free DA in the aqueous phase of the cream.
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  • YUKIO SATO, TADAHIKO CHIBA, YASUO SUZUKI
    1985 Volume 33 Issue 9 Pages 3935-3944
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The interaction between eosin 5-isothiocyanate (EITC) and human erythrocyte ghosts has been studied by means of fluorescence and absorption difference spectroscopy. The fluorescence quenching data of the ghost-EITC system showed a biphasic change. EITC molecules bound to band 3 proteins and adsorbed on ghost membranes are responsible for this biphasic change. Binding of EITC molecules to the ghosts leads to a redshift and hypochromism in the visible region. Consequently, the difference spectrum shows a positive peak and two negative ones at 540, 517, and 483 nm from the longer wavelength side. The intensities of these peaks change heterogeneously under various conditions, reflecting the contributions of xanthene and phenyl chromophores bound to band 3. It was considered that the conformational structure of EITC binding sites is sensitive to temperature, showing a transition at about 30°C. The reactivity of EITC molecules with band 3 at temperatures below 30°C is different from that above 30°C. It is inferred that the EITC binding sites on band 3 are identical with the modifier sites.
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  • TAKASHI OHSAWA, HIROSHI MIURA, KIYOSHI HARADA
    1985 Volume 33 Issue 9 Pages 3945-3952
    Published: September 25, 1985
    Released on J-STAGE: March 31, 2008
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    In order to improve the encapsulation efficiency (EN%) of a water-soluble drug in liposomes formed by the freeze-thawing (FT) method, the influence of preparation conditions was examined in detail using L-asparaginase (A-ase) as a model drug. The results were compared with those obtained by the thin film (hydration) method. It became clear that lower ionic strength in the suspension medium, gentle shaking after thawing, higher concentration of phospholipid and a relatively low concentration of A-ase were preferable to obtain higher EN% in the FT method. To confirm these results, other drugs of various molecular weights, cyanocobalamin, inulin and glucose, were encapsulated under controlled preparation conditions so as to obtain high EN%. High EN% values of from 40% to 60% (evaluated by the gel filtration method) were obtained. The influence of the phospholipid composition was also examined using phosphatidylcholine (PC), a mixture of PC and stearylamine, and a mixture of PC and dicetylphosphate. All of them gave lower EN% than yolk phospholipid (YPL). The mechanism of liposome generation is discussed on the basis of the results obtained.
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