YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
99 巻, 3 号
選択された号の論文の16件中1~16を表示しています
  • 北澤 式文, 上能 伊公雄, 横山 祥子, 蓑内 徳蔵, 大野 明洋, 岡田 寿太郎
    1979 年 99 巻 3 号 p. 221-227
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    In the J.P.IX disintegration test for enteric-coated tablets, the tablets are tested for 120 min in the first fluid (pH 1.2) prior to the test in the second fluid (pH 7.5). In clinical medicine, tablets are often administered to patients under fasting conditions and to partial or total gastrectomy patients. It is well known that the gastric emptying rate in these conditions is faster than in normal condition. Therefore, to clarify the effects of a shortened test period in the first fluid on entericcoated tablets disintegration time and coefficient of variation (C.V.), three different test periods (120, 30 and 0 min) were used. These tests were conducted on 17 enteric-coated tablets on the market. Two lots of these preparations failed to disintegrated completely under all of the test conditions. The disintegration time of these tablets in the second fluid obtained with the first fluid was generally faster compared to that obtained without the fluid. When the tablets were tested with the first fluid for 30 or 120 min, disintegration time was approximately constant. Moreover, in some preparations the disintegration time obtained without disks was markedly increased and they failed to disintegrate completely. The effect of test period in the first fluid on the C.V. in disintegration time was not negligible and the C.V. was changed irregularly by alterations of the test period. Usually, but not always, it was found that adherence of the test tablets to disks or test equipment tends to increase disintegration time and C.V.
  • 木村 勝彦, 長岡 正男, 中沢 修一, 扇谷 正三郎
    1979 年 99 巻 3 号 p. 228-234
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    Examinations were made on the N-C cleavage of nitrogen-derivatives of piperidine by the 9000×g supernatant of mouse and rat liver in vitro. The derivatives examined were N-methylpiperidine (I), N-ethylpiperidine (II), N-(2-hydroxyethyl) piperidine (III), N-carboxymethylpiperidine (IV), N-cinnamylpiperidine (V), and three kinds of Mannich base of piperidine. Results obtained may be summarized as follows : 1) The rat liver supernatant showed greater cleavage activity than the mouse liver supernatant for all the derivatives examined. The order of N-C cleavage of these derivatives was approximately the same with the liver of both animals. 2) Cleavage of the N-ethyl derivatives (I, II, III, and IV) was small with both mouse and rat liver supernatants, and that of the Mannich bases was greater. V showed cleavage of a degree intermediate of these two. 3) Phenobarbital induced cleavage activity of both mouse and rat liver supernatant, while 3-methylcholanthrene had no effect on the cleavage with the exception of the Mannich bases in which it showed a slight induction. 4) Inhibition of cleavage activity to a considerable degree was seen by pretreatment of mice and rats with SKF-525A.
  • 木村 勝彦, 長岡 正男, 我妻 仁, 扇谷 正三郎
    1979 年 99 巻 3 号 p. 235-239
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    Values of pKa, Km, and Vmax, and percentage of non-dissociated type, and distribution coefficient in organic solvents were measured in N-derivatives of piperidine ; N-methyl-, N-(2-hydroxyethyl)-, N-carboxymethyl-, and N-cinnamyl-piperidines, 3-methyl-4-piperidinobutan-2-one, 1-phenyl-3-piperidinopropan-1-one, and 1, 3-diphenyl-4-piperidinobutan-2-one, and correlation between these values and N-C cleavage of these derivatives was discussed. In general, derivatives having smaller pKa and Km values and those having larger percentage of non-dissociated type, distribution coefficient, and Vmax values were found to have greater tendency for cleavage.
  • 浜川 博司, 高柳 法康, 中神 啓二, 小針 定美, 清水 武
    1979 年 99 巻 3 号 p. 240-251
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    The anti-inflammatory and other related properties of N-cyclohexyl-N'-(2-methoxy-5-chlorophenyl) benzamidine hydrochloride monohydrate (HG-70), which was selected as the most potent anti-edematous and low toxic new compound among 93 amidines, were investigated to determine profile and mode of action. HG-70 showed marked inhibitory activity on scald paw edema (delayed response) in rats. It also possessed non-specific anti-edematous activity more potent than that of well known anti-inflammatory drugs tested on paw edema induced by carrageenin, serotonin, mustard, trauma, formalin, yeast and bradykinin and skin edema with Punch method. Furthermore, HG-70 showed somewhat weaker inhibitory activity on paper disk-induced granuloma test and granuloma pouch test than phenylbutazone. HG-70 markedly inhibited compound 48/80-induced degranulation of rat mesenterium mast cells. HG-70 inhibited heat-induced hemolysis of rat erythrocytes and collagen-induced platelet aggregation and moderately inhibited histamine-induced capillary permeability. On the other hand, the inhibitory activity of HG-70 as well as sodium salicylate, on carrageenin edema was somewhat suppressed by adrenalectomy and hypophysectomy. HG-70 effected a decrease in the adrenal ascorbic acid and an increase in the plasma corticosterone levels in rats. These results suggest that the anti-inflammatory activity of HG-70 may be primarily due to its inhibitory activity on the release of endogenous inflammatory substances in injury tissues because of its membrane stabilizing action and its inhibitory activity on inflammatory substances and increased vascular permeability and to partly involve stimulation of the pituitary-adrenal system.
  • ヒキノ ヒロシ, 佐藤 博, 山田 千鶴子, 今野 長八, 大泉 康, 遠藤 勝也
    1979 年 99 巻 3 号 p. 252-263
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    The pharmacological properties of raw Aconitum roots from Niigata (1), Hokkaido (2) and China (3) and their processed preparations (4, 5 and 6, respectively) were examined in comparison with their constituents, aconitine (AC) and benzoylaconine (BA) (doses expressed in per kg p.o. in vivo, unless otherwise stated, and per ml in vitro). On blood pressure in rats, 1, 3 (0.1 g i.v.) and AC (50μg i.v.) exhibited a weak temporary hypotensive action, while 2 (0.1 g i.v.) elicited a diphasic reaction, a remarkable hypertension followed by hypotension. 4-6 (0.1 g i.v.) mediated marked temporary hypertensive action. In the isolated right atria of guinea pigs, 1-3 (10-6-10-5g) showed positive inotropic and chronotropic action. Further, 1-3 (10-4g) and AC (10-7g) exhibited these actions followed by negative inotropic action and disorder of the heart rate. In the isolated ileum of guinea pigs, 1-3 (10-4g) and AC (10-6g) caused weak contraction which was antagonized by atropine. In the isolated vas deferens of guinea pigs, 1-6 (10-4g), AC and BA (10-5g) produced no contraction, and had no effect on contraction induced by norepinephrine or tyramine. In the isolated hypogastric nerve-vas deferens of guinea pigs, the isolated mesenteric nerve-jejunum of rabbits and the isolated phrenic nerve-diaphragm of rats, 1-3 (10-4g) and AC (10-6g) inhibited responses induced by electrical stimulation of the corresponding nerves. In mice, 1-2 (0.1-1.0g) showed analgesic activity in the tail pressure method and 1-3 in the acetic acid-induced writhing method. In mice, 1-3 (0.1-1.0g) potentiated hexobarbital anesthesia. In mice, 1-3 (0.1-1.0g) and AC (1 mg) reduced revolution of the wheel cage. In mice, 3 (1.0 g) and AC (1 mg) showed hypothermic action by 1.5-2°. In mice, 1-3 (0.1-1.0g) inhibited the stress-induced ulcer production.
  • 高平 正行, 近藤 嘉和, 草野 源次郎, 野副 重男
    1979 年 99 巻 3 号 p. 264-272
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    Five new spirostane steroids were isolated from a kind of crude drug, "Senshokushichikon."They were characterized as 3-epi-diosgenin 3-β-D-glucopyranoside (I), 3-episceptrumgenin 3-β-D-glucopyranoside (II), 3-epi-ruscogenin (III), 3-epi-neoruscogenin (IV), and 3-epi-diosgenin (V). They are the first examples of naturally occurring 3α-hydroxyspirost-5-enes derivatives.
  • 大原 秀人, 小野 英樹, 塩尻 博之, 大郷 利治
    1979 年 99 巻 3 号 p. 273-279
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    The effects of neomycin (NM) and chenodeoxycholic acid (CDCA) feeding on biliary lipids composition, fecal excretion of bile acids and plasma cholesterol levels were studied in hamsters. Sixteen male hamsters were fed diets containing NM (0.5, 1 and 2%) and CDCA (1%) for 9 days under the experimental design using the two-way layout. After dosing of two drugs, blood samples were obtained following the collection of hepatic bile juice for one hour under urethan anesthesia. Feces were collected from each experimental group for 24 hours before bile collection. Feeding CDCA and NM had no effect on the concentration of biliary lecithin, cholesterol and total bile acid, but the two drugs affected considerably bile acid composition. By CDCA feeding, biliary CDCA and lithocholic acid (LCA) increased significantly, whereas cholic acid (CA) and deoxycholic acid (DCA) decreased. NM feeding depressed the increase of LCA effected by CDCA feeding, DCA was not detected or in trace amounts in all biles from NM-fed hamsters. In feces from CDCA-fed hamsters, a great amount of LCA was detected. By NM feeding, the fecal concentration of the secondary bile acids (LCA and DCA) decreased markedly, while the primary bile acids (CDCA and CA), which could not be detected in feces from the basal diet fed group, were detected. Plasma cholesterol levels were decreased significantly by both drugs.
  • 高橋 浩, 富田 考一, 野口 博美, 乙益 寛隆
    1979 年 99 巻 3 号 p. 280-284
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    (±)-erythro-2-Methylamino-1, 2-diphenylethanol was resolved by using D-10-camphorsulfonic acid, and the optically active compound (I) showing a specific rotation of +39.8°, was prepared. Compound (I) was derived from (1S, 2R)-(+)-erythro-2-amino-1, 2-diphenylethanol (II) and its absolute configuration was determined as (1S, 2R). The chiral hydrazone compounds (Va and Vb) were obtained by condensation of methyl pyruvate and ethyl phenylglyoxylate with (1S, 2R)-(+)-erythro-2-(1-methyl-hydrazino)-1, 2-diphenylethanol (IV). Reduction of the C=N group in these compounds was carried out using Pd-C catalyst in ethanol, followed by hydrogenolysis of the N-N linkage using the same catalyst in hydrochloroacidic ethanol solution, and hydrochlorides of amino acid ester and I were obtained. Alanine and phenylglycine formed by hydrolysis of amino acid esters afforded S configuration with optical purity of 10 and 1.9%, respectively. More than 95% of the optical purity of I was conserved during chiral amination of the ketoesters.
  • 安田 正秀, 藤田 直, 水谷 泰久
    1979 年 99 巻 3 号 p. 285-289
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    To examine the effect of vitamin E on plasma and liver lipid content and on the growth of rats, vitamin E (0.1, 1.0, 10, or 50 mg/kg) was injected intraperitoneally once a day for one month. Weight gain in vitamin E-injected rats showed a tendency to decrease in comparison to control animals, however, the liver body/weight ratios were not altered. Fatty acid composition in total rat liver and plasma lipids was not affected by the administration of vitamin E. Vitamin E administration effected no changes in free fatty acid and total cholesterol concentration in the liver and plasma. On the other hand, triglyceride contents in the liver decreased in proportion to the doses of vitamin E, namely the reduction was about 25% and 35% by the administration of vitamin E in a dose of 10 and 50 mg/kg/day for one month, respectively. Concentration of plasma triglycerides increased by the administration of Tween 80 (4 mg/kg/day, for one month), however the increased triglycerides decreased and recovered to the control levels by the treatment with vitamin E (50 mg/kg/day). The present results suggest that vitamin E may have a lowering effect on triglycerides in the rat liver.
  • 坂口 武一, 田辺 信三, 大谷 武司
    1979 年 99 巻 3 号 p. 290-294
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    The structure of a pigment I produced from guanidine with 9, 10-phenanthraquinone and 1-naphthol in the presence of alkali was investigated. Pigment I was found to be a ternary product formed by the condensation of one equivalent each of guanidine, 9, 10-phenanthraquinone, and 1-naphthol. The molecular formula and IR spectrum of I were identical with those of pigment II isolated from the reaction with 4-chloro-1-naphthol instead of 1-naphthol. Pigment I could be derived from 2-amino-1H-phenanthro [9, 10-d] imidazole (V) which was obtained as a fluorescent product in the reaction of guanidine or mono-substituted guanidines with 9, 10-phenanthraquinone. Therefore, the structure of pigment I was concluded to be N-(1'H-phenanthro-[9, 10-d] imidazolyl)-1, 4-naphthoquinone monoimine. Thin-layer chromatography also proved that pigment I was formed in the reaction mixture of 9, 10-phenanthraquinone, 1-naphthol, and mono-substituted guanidines, regardless of the kinds of guanidines. Based on these results, the mechanism of this color reaction was discussed.
  • 竹原 光教, 小池 満
    1979 年 99 巻 3 号 p. 295-301
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    To date, the apparent membrane partition coefficient (Pa) has been obtained by an apparent decrease of concentration in a membrane-solution system. However, a part of the solute molecules absorbed by the membrane seems to be in the immobile state because the molecules are tightly restricted by the membrane component. The partition coefficient which is related to the diffusion must be defined by the mobile solute only. We may call the partition coefficient defined by the mobile solute"reversible partition coefficient (Pr)", and the partition coefficient defined by the immobile solute"irreversible partition coefficient (P1r)". The Pr can be obtained by 2 step experiments (absorption of solute by, and release of solute from the membrane). Theories on the Pr of the membrane and the porous membrane are proposed here. Silicone rubber membrane was prepared from the silicone rubber compound (SRC : Shinetsu Kagaku KE-102RTV) and concentration dependence of the Pa and Pr were measured on the SRC-membrane-salicylic acid (SA) solution system. The Pa and Pr values decreased with an increase in SA-concentration and the Pa value approached the Pr value. On the other hand, the Pa and Pr values were measured on the benzene-SA-solution and silicone oil-SA-solution systems and it is clear that the Pa value is nearly equal to the Pr value in the liquid-liquid system. The Pr value of the SRC-membrane is 6 times greater than the Pr value of the silicone oil. The permeation of SA through the SRC-membrane was measured on the SA-solution-memberane-water system, the results were compared with the simulation results carried out on the basis of the theory and technique reported before (Ref. 5 and 6), and good agreements were obtained between them. The experimental results disagreed with the simulation results which were obtained by using the Pa value.
  • 竹原 光教, 小池 満
    1979 年 99 巻 3 号 p. 302-307
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    The diffusion obstruction effect caused by the impermeable particle was tested, using glass beads (GB) dispersed in the silicone rubber membrane and drug release from the O/W emulsion was measured by varying the volume fraction (VF) of oil phase (droplet phase). Permeability of salicylic acid (SA) through the membrane and the effective diffusion coefficient of SA were decreased with an increase in the VF of GB. The obstruction effect was proved by the above mentioned phenomena, but no size effect of GB was observed. Wang's equation may be useful for these systems. The drug release from emulsion was decreased with an increase in the VF of oil phase and was compared with the theoretically releasable amount (TQ3) of SA which can be calculated from the volume of donor, membrane, and receptor phase and the partition coefficients of membrane and droplet. The obstruction effect of droplet on the drug release from emulsion was also proved by the decreasing of the ratio of percent release and TQ3 with an increase in the VF of oil phase. In designing creams or emulsions, we must take into account the VF of oil phase (droplet phase) which relates to the drug release from the preparations.
  • 渡辺 康, 本橋 清, 米田 良蔵, 三井 美澄, 佐野 倫男
    1979 年 99 巻 3 号 p. 308-314
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    We studied the relationship between bioavailability and incidence of side reaction of commercial erythromycine tablets. Bioavailability of the preparations was determined by measuring area under the serum concentration of the drug-time curve (AUC), peak height and time to attain the peak in serum concentration. Frequency of appearance of side reaction was surveyed by questionaire to each volunteer. Five kinds of commercial tablets were administered to groups of 20 healthy female volunteers, and bioavailability and frequency of side reaction were investigated. A correlation between the frequency of side reaction and relative AUC, set as 100% in the case of C product, was observed. Four volunteers complained of side reaction in the case of C product, while in the case of A product (relative AUC 4%), and nobody complained of side reaction. These relationships were also observed between the frequency side reaction and the peak height and/or the time to attain the peak of drug concentration. When test tablets containing an equivalent amount of the drug and coated with various enteric coating substances of different dissolution pH were administered to the same volunteers, the same inclination was noted. Average in the peak height of serum concentration was higher in volunteers who complained of gastralgia than in volunteers who did not complain of any side reaction.
  • 太幡 利一, 田中 満男, 余田 和明, 飯尾 利弘
    1979 年 99 巻 3 号 p. 315-318
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    The hypocholesterolemic activity of phytosterol was studied using rats on a 3%-cholesterol containing diet. Rats were intravenously injected for 5 days with emulsion of saline-alubumin containing phytosterol and the plasma and liver cholesterol level was decreased. The decreasing in liver cholesterol level was accampanied by an increase of bile acid contents excretion without change in composition, and the injected phytosterol was accumulated in liver mainly. The cholesterol level in liver subcellular fractions after phytosterol treatment was decreased most significantly in soluble fraction, but little or not in microsome, although most of phytosterol in the liver cells was distributed in this fraction. These results suggest that the absorbed phytosterol has the ability to decrease the cholesterol level in liver by means of the enhancement of convertion from cholesterol to bile acid.
  • 赤田 良信, 河野 貞子, 棚瀬 弥一郎
    1979 年 99 巻 3 号 p. 319-322
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    High-speed liquid chromatography employing an ultraviolet photometric detector (254 nm) was applied to the separation determination of hippuric acid, p-hydroxyphenylacetic acid, toluoylglycines, p-hydroxybenzoic acid and benzoic acid in human urine. Reversed-phase partition chromatography was carried out on a Zorbax CN column with 0.1M HClO4 (pH 3.5)-MeOH (75 : 25, v/v) as the eluent system with a Shimadzu Du Pont LC 2 liquid chromatograph. This method obviates the necessity of samples for isolation or derivation of these acids before assay. The only pretreatment necessary is extraction of samples from human urine with ethyl acetate. The accuracy of this method was found to be less than ±1% and the limits of detection were shown.
  • 高木 修造, 伊藤 幸江
    1979 年 99 巻 3 号 p. 322-324
    発行日: 1979/03/25
    公開日: 2008/05/30
    ジャーナル フリー
    Some modified methods are reported for easier quantitative determination of three major"senso"-bufosteroids ; resibufogenin, cinobufagin and bufalin. Satisfactory results were obtained by gas liquid chromatography analyses without tetramethylsilane pretreatment and by thin-layer chromatography analyses using methyltestosterone as internal standard.
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