著者

FURUSE KAZUMARO ISHIZEKI CHUICHI IWAHARA SHIGEO

出版者

公益社団法人日本薬学会

雑誌

Journal of pharmacobio-dynamics (ISSN:0386846X)

巻号頁・発行日

vol.6, no.6, pp.359-372, 1983-06

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The spermicidal activities of seven nonionic surfactants against human spermatozoa were objectively determind by a statistical method, and two types of ionic surfactants were also studied for purposes of comparison. The nonionic surfactants, p-menthanylphenyl poluoxyethylene adducts used in this work were synthesized from turpentine oil. These surfactants were used in the experiment after a careful confirmation of their chemical composition and molecular weight distribution. The spermicidal activities of the surfactants in terms of minimum concentrations to accomplish irreversible immobilization of all sperms in zero time was, in decreasing order, nonionic, cationic and anionic. When the most commonly used nonionics alone were considered, the sequence of decreasing spermicidal potency was isononylphenyl polyoxyethylene (9.0) ether (nonoxynol-9), p-menthanylphenyl polyoxyethylene (8.8) ether (menfegol), isooctylphenyl polyoxyethylene (9.0) ether(octoxynol-9).The surface tension and wetting time of these surfactants were determined with a view to finding physico-chemical measures of their spermicidal activity. In the statistical analysis regarding all the nine surfactants, there was a significant correlation (p<0.05) between spermicidal potency and critical micelle concentration (cmc) whereas there was no significant relationship between spermicidal potency and cmc regarding the seven nonionics. There was again no significant correlation between spermicidal potency and wetting time in all but nonionics with a common hydrophobic structure. As neither surface tension nor wetting time appeared to be a valid factor, general measure of spermicidal potency of nonionic surfactants, the partition ratios between n-octanol or n-hexane and water was determind. As a result, it was revealed that there was a significant correlation (p<0.05) between spermicidal potency and partition coefficient, when four types of nonionic surfactants with different hydrophobic group, which were chosen from among the seven nonionics, were tested with n-hexane.The close relationship between spermical activity and partition coefficient suggests that the spermicidal activities of these surfactants are associated with their structural affinity to the lipids of spermatozoal cell membrane.

著者

MINEO SANEYOSHI MOTOKO INOMATA TERUAKI SEKINE AKIO HOSHI FUMIKO FUKUOKA

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.1, no.3, pp.168-174, 1978 (Released:2008-02-21)

参考文献数

12

被引用文献数

6 6

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Reaction of S-benzylthioisothiouronium hydrochloride with 6-mercaptopurine (1), 9-β-D-ribofuranosyl-6-mercaptopurine (2), 6-thioguanine (3) and 9-β-D-ribofuranosyl-6-thioguanine (4) afforded corresponding benzyl disulfide derivatives (5-8) in good yield. These compounds were converted easily to parent mercapto derivatives when they were treated with various reducing agents such as β-mercaptoethanol. Antitumor activity of compound 5 was higher than that of 1 both in ascites Sarcoma 180 and in Nakahara-Fukuoka sarcoma systems. However, toxicity and immunosuppressive activity of compound 5 and 6 were higher than those of 1 and 2, respectively.

著者

FUMIHIKO KANZAWA AKIO HOSHI KAZUO KURETANI

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.3, no.8, pp.390-394, 1980 (Released:2008-02-19)

参考文献数

20

被引用文献数

1 1

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5-Fluorouracil-resistant cell line designated as L5178Y/FU was established in this experiment. This is one of the colonies derived from the subculture which acquired resistance to 5-fluorouracil by passaging the L5178Y cells through ten successive episodes of culture in Fischer's medium containing 5-fluorouracil, in which each 5-fluorouracil treatment was followed by recovery intervals. The resistance of this line is about 80-fold that of the IC99 of 5-fluorouracil, and also shows a cross resistance to both 5-fluorouridine and 5-fluoro-2'-deoxyuridine. 5-Fluoro-2'-deoxyuridine resistant subline designated as L5178Y/FUdR was also isolated from the subculture which acquired resistance to 5-fluoro-2'-deoxyuridine by using the same selection procedure. The resistance of this line is about 650-fold that of the IC99 of 5-fluoro-2'-deoxyuridine, and shows a partial cross-resistance to 5-fluorouridine, but not to 5-fluorouracil.

著者

FUMIHIKO KANZAWA YUKA MATSUSHIMA JUNICHI ISHIHARA AKIO HOSHI TAKEO OHBA KENZO WATANABE

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.9, no.8, pp.688-693, 1986 (Released:2008-02-19)

参考文献数

16

被引用文献数

5 5

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A series of twenty six 5'-substituted FdUMP (5-fluoro-2'-deoxyuridine 5'-monophosphate) have been evaluated for their inhibitory effects on the proliferation of murine lymphoma L5178Y cells sensitive or resistant to FUdR (5-fluoro-2'-deoxyuridine). 5'-Octylphenylene-FdUMP was the most active among these active derivatives against the parent cell line (L5178Y/P). Several other FdUMP derivatives also proved as potent as FUdR in their antiproliferating activity on the L5178Y/P cell line. Activity of these derivatives was decresed considerably by a substituent with a long aliphatic chain and the introduction of acyl groups on the C-3' position. Eicosyl-FdUMP was found to show no or low cross-resistance on the L5178Y/FUdR subline which was about 19000-fold resistant to FUdR compared with the parent cell line. This derivative might penetrate cell membrane in an intact form and be converted into FdUMP by a phosphodiesterase inside the cell, because an anabolic enzyme, deoxyuridine kinase, was defective in cells of the L5178Y/FUdR subline. The derivatives were promising as antitumor agents for the treatment of relapsed patients following 5-fluorouracil therapy.

著者

Tatsuya TSUJI Norimasa KANEDA Kunio KADO Teruo YOKOKURA Tadashi YOSHIMOTO Daisuke TSURU

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.14, no.6, pp.341-349, 1991 (Released:2008-02-19)

参考文献数

25

被引用文献数

73 97

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A rat serum enzyme that catalyzes the conversion of a pro-drug, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), to an anticancer drug, 7-ethyl-10-hydroxycamptothecin (SN-38), was purified and its properties were characterized. The enzyme was purified by column chromatography on diethylaminoethyl Toyopearl 650M, QAE-Sephadex, Sephadex G-150, Con A-Sepharose and high performance liquid chromatography with an ion-exchanger column. It was most active at pH 7.5 and was stable at pH 4-9 for 1 h at 30°C. The molecular weight was estimated to be 60 and 57 kDa by gel filtration and sodium dodecylsulfate-polyacrylamide gel electrophoresis methods, respectively, and the isoelectric point was 4.6, as determined by isoelectric focusing. The Km value for CPT-11 was 0.28 μM. This enzyme was inhibited by diisopropyl phosphorofluoridate (DFP) and phenylmethanesulfonyl fluoride (PMSF) but insensitive to eserine, p-chloromercuribenzoate (PCMB) and ethylenediaminetetraacetate (EDTA). The enzyme also hydrolyzed p-nitrophenylacetate (p-NPA), a commonly used substrate for esterases, but was not active toward acetylcholine, suggesting that the enzyme is a carboxylesterase [EC 3.1.1.1]. During the hydrolyses of CPT-11 and p-NPA, an initial burst phenomenon similar to that found in the α-chymotrypsincatalyzed hydrolysis of p-NPA was observed. Kinetic analysis revealed that the deacylation of the enzyme is the rate-limiting step in substrate hydrolysis. This enzyme was found to also split other ester derivatives of SN-38 besides CPT-11.

著者

TAKEHIKO KUNIMOTO KAZUO NITTA TOMIKO TANAKA NOBUAKI UEHARA HIROYASU BABA MIEKO TAKEUCHI TERUO YOKOKURA SEIGO SAWADA TADASHI MIYASAKA MASAHIKO MUTAI

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.10, no.3, pp.148-151, 1987 (Released:2008-02-19)

参考文献数

7

被引用文献数

7 15

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The antitumor activity of a new camptothecin derivative, SN-22, was evaluated by using various murine tumors. SN-22 showed strong activity against the ascites tumors Ehrlich carcinoma, MM46, CCM, L1210, L5178Y, P388, Meth A, and B16 melanoma. In particular, the maximum increase in life span values for Ehrlich, MM46 and CCM were as high as 253-606% and many mice were cured of these tumors. The effect of SN-22 against solid tumors was also determined. The inhibition ratios were higher than 70% for MM46 and L5178Y. The LD50 of SN-22 in ICR mice was about 1.5 times that of the parent camptothecin.

著者

KITAZATO KENJI TAKEDA SETSUO UNEMI NORIO

出版者

公益社団法人日本薬学会

雑誌

Journal of pharmacobio-dynamics (ISSN:0386846X)

巻号頁・発行日

vol.5, no.10, pp.803-810, 1982-10

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1,3,3,5,5-Pentaziridino-1-thia-2,4,6-traiza-3,5-diphosphorine-1-oxide (SOAz), a new antitumor agent, was evaluated for antitumor activity against various mouse- and rattumor systems. The optimal treatment regimens of SOAz (i.p.) gave 262% and 134% increase in life span (ILS) in mice P338 leukemia and L1210 leukemia implanted intraperitoneally, respectively, and 239% ILS in rats with Yoshida sarcoma of which 86% survived for 60 d after intraperitoneal tumor implantation. The compound showed a definite activity against Lewis lung carcinoma implanted intravenously. The compound also exhibited 80-100% inhibition of tumor local growth in all of four experimental tumor systems used in the present study. In contrast to cyclophosphamide, SOAz was active against B16 melanoma and Meth A, and demonstrated high activity against a subline of L1210 leukemia resistant to cyclophosphamide.

著者

KAZUO IGARASHI FUMIYO KASUYA MIYOSHI FUKUI

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.6, no.8, pp.538-550, 1983 (Released:2008-02-19)

参考文献数

16

被引用文献数

3 4

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The metabolism of dibucaine was studied in the rat, rabbit and man. A total of ten basic metabolites other than dibucaine were detected in the urine samples of three species by thin-layer chromatography (TLC) and gas chromatography (GC), and structures of these metabolites were identified by comparison of the properties given by TLC, GC and gas chromatography-mass spectrometry (GC-MS) with those of authentic compounds. Four of these metabolites were new metabolites which were found in the rabbit or human urine ; two were identified as the 2', 3'-dihydroxybutoxy product (M-6, diol) and its N-deethyl product (M-2), and others were identified as the 2'-hydroxyethoxy product (M-8, alcohol) and its N-deethyl product (M-3). One of the two hydroxyl groups on M-5 was at 6-position on the quinoline ring, while another was assumed to be at 3'-position on the O-alkyl side chain. There were apparent species differences with regard to the major metabolites found in each species ; i.e. M-10 and M-5 in rat, M-6 and M-4 in rabbit, and M-8 and M-4 in man. Small amounts of the conjugated basic metabolites were observed in the urine of all three species. The new metabolic pathways to the diols (M-2 and M-6) or the alcohols (M-3 and M-8) were also discussed.

著者

AKIO NISHIURA TERUO MURAKAMI YUTAKA HIGASHI NOBORU YATA

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.10, no.3, pp.135-141, 1987 (Released:2008-02-19)

参考文献数

22

被引用文献数

10 12

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The mechanism of interorgan variation in tissue distribution of quinidine was investigated from a viewpoint of binding characteristics to phospholipids and the composition of phospholipids in various tissues. The order of binding of quinidine to an individual standard phospholipid, expressed as a product of the association constant (K) and the number of binding sites (n), was : phosphatidyl ethanolamine (PhE)<dipalmitoyl phosphatidyl choline (saturated PhC)≥phosphatidyl choline (unsaturated PhC)<phosphatidyl inositol (PhI)<phosphatidyl glycerol (PhG)<phosphatidic acid (PhA)<phosphatidyl serine (PhS). Thus, quinidine was found to bind preferentially to acid phospholipids such as PhS, PhA, PhG, and PhI. The greatest binding was obtained in PhS among the various phospholipids and was more than 300-fold that of neutral phospholipids such as PhC and PhE. The concentration of individual components of phospholipids in the lung, kidney, liver and heart was determined using a two dimensional thin-layer chromatography. The concentration of PhS, highly responsible for the quinidine binding to phospholipids in each tissue, was ranked in the following order : heart<liver<kidney<lung. The contribution of PhS to quinidine binding was more than 86% in all tissues. A good correlation between the concentration of PhS in each tissue and the Ct/Cp ratio in vivo was obtained (r=0.984). Thus, it was concluded that the tissue distribution of quinidine in vivo depended on the composition of phospholipids in tissues and that a determinant of interorgan variation in the tissue distribution of quinidine was the concentration of PhS in the tissues.

著者

MAMORU SUEKAWA ATSUSHI ISHIGE KAZUNORI YUASA KAZUHIKO SUDO MASAKI ABURADA EIKICHI HOSOYA

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.7, no.11, pp.836-848, 1984 (Released:2008-02-19)

参考文献数

9

被引用文献数

91 180 242

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General pharmacological studies were performed on (6)-gingerol and (6)-shogaol whhich are the pungent constituents of ginger (Zingiber officinale ROSCOE). Intravenous (i.v.) administration of (6)-gingerol (at 1.75-3.5 mg/kg) or (6)-shogaol (at 1.75-3.5 mg/kg) and oral administration of them (at 70-140 mg/kg) produced an inhibition of spontaneous motor activity, an antipyretic and analgesic effects, prolonged hexobarbital-induced sleeping time, and these effects of (6)-shogaol were mostly more intensive than that of (6)-gingerol. (6)-Shogaol showed an intense antitussive effect in comparison with dihydrocodeine phosphate. In the electro-encepharogram of cortex, the low amplitude fast wave pattern was observed for 5 min after i.v. administration of (6)-shogaol, and then changed to the drowsy pattern, which was restored after 60 min. In the gastro-intestinal system, (6)- shogaol intensively inhibited the traverse of charcoal meal through the intestine in contrast with (6)-gingerol after i.v. administration of 3.5 mg/kg, but (6)-shogaol facilitated such an intestinal function after oral administration of 35 mg/kg. Both (6)-shogaol and (6)-gingerol suppressed gastric contraction in situ, and the suppression by the former was more intensive than that by the latter. In the cardiovascular system, both (6)-shogaol and (6)-gingerol produced depressor response at lower doses on the blood pressure. At high doses, both drugs produced three phase pattern.

著者

Hirofumi MARUYAMA Keiko YAMAZAKI Sayuri MUROFUSHI Chihiro KONDA Tetsuro IKEKAWA

出版者

The Pharmaceutical Society of Japan

雑誌

Journal of Pharmacobio-Dynamics (ISSN:0386846X)

巻号頁・発行日

vol.12, no.2, pp.118-123, 1989 (Released:2008-02-19)

参考文献数

12

被引用文献数

22 35

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Antitumor activity of Sarcodon aspratus (BERK.) S. ITO and Ganoderma lucidum (FR.) KARST. was investigated. Methanol and aqueous extracts of these Japanese mushrooms were tested for antitumor activity against solid type of sarcoma 180 by intraperitoneal or oral administration. The aqueous extract was remarkably effective for inhibition of tumor growth, but the methanol extract was not. The fraction of molecular weight more than 10000 had a high inhibitory activity against the tumor growth, but the fraction of molecular weight less than 10000 did not. Fractionation was carried out by using an ion-exchanger, and fraction S-4 having the highest carbohydrate content had the highest antitumor activity by intraperitoneal administration.

著者

TAKENAGA MITSUKO HIRAI AIZAN TERANO TAKASHI TAMURA YASUSHI KITAGAWA HARUO YOSHIDA SHO

出版者

公益社団法人日本薬学会

雑誌

Journal of pharmacobio-dynamics (ISSN:0386846X)

巻号頁・発行日

vol.10, no.5, pp.201-208, 1987-05

被引用文献数

5 22

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The in vitro effect of cinnamic aldehyde, a main component of Cinnamomi Cortex, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets was studied. Cinnamic aldehyde reduced platelet aggregation of both platelet rich plasma and washed platelets, dose-dependently. This compound also decreased the formation of the metabolites of AA such as thromboxane B_2 (TXB_2), 12-hydroxy heptadecatrienoic acid and 12-hydroxyeicosatetraenoic acid in collagen-stimulated washed platelets. The conversion of exogenous [^<14>C] AA to cyclooxygenase metabolites or 12-lipoxygenase metabolite was not altered significantly by the addition of cinnamic aldehyde. On the other hand, collagen-induced released of [^<14>C] AA and its metabolites from washed platelets prelabeled with [^<14>C] AA was markedly reduced by the addition of cinnamic aldehyde. These results suggested that cinnamic aldehyde suppressed the release of AA from platelet membrane phospholipids and then reduced the formation of thromboxane A_2. This inhibitory effect of cinnamic aldehyde on AA release and TXB_2 formation may contribute to reduced platelet aggregation.

著者

LANAO Jose M VICENTE M. Teresa SAYALERO M. Luisa DOMINGUEZGIL Alfonso

出版者

公益社団法人日本薬学会

雑誌

Journal of pharmacobio-dynamics (ISSN:0386846X)

巻号頁・発行日

vol.15, no.5, pp.203-214, 1992-05

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A program adapted for use on microcomputers (DCN) has been developed which permits one to perform operations of numerical convolution and deconvolution using polyexponential functions, that are often implemented in pharmacokinetic analysis. The program is written in Microsoft GWBASIC and can be used in personal computers with no modification. The user supplies information relating to the coefficients and exponentials defining the polyexponential equation of the response and weighting functions and the program performs the deconvolution operation by numerical integration using trapezoidal rule and provides numerical and graphic information concerning the input function. The program can be applied to the deconvolution of many linear pharmacokinetic systems and allows one to solve problems related to drug release, absorption, distribution, as well as others. Additionally, the program is able to perform the convolution operation if information about the input and weighting functions and is also able to simulate pharmacokinetic processes. The efficacy of the program was evaluated by comparison with several deconvolution algorithms, in particular that proposed by Veng-Pedersen and Iga.