巻号一覧
106 巻, 2 号
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永井 恒司1986 年 106 巻 2 号 p. 99-109
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーThe recent advances in pharmaceutical technology have been promoted in a strong relation to taking the data to prove the efficacy and safety in drug development activities and also to designing new dosage forms with high stability and suitable bioavailability.
The development of pharmaceutical technology may be divided historically as follows: a) pre-pharmaceutical (without consideration on bioequivalence); b) first generation (conventional or regular preparations); c) second generation (regular controlled release preparations); d) third generation (precisely controlled release preparations, i. e., drug delivery systems (DDS) and transdermal therapeutic systems (TTS)); e) fourth generation (drug targeting, missile). We can find materialized ones on d) the third generation, as it may be promising on e) the fourth generation in future. In a wide sense, the above-mentioned d) and e) are classified into drug delivery systems (wide-DDS), as the former may be the first generation of wide-DDS and the latter the second generation of wide-DDS.
Noticeable ones in recent advances in pharmaceutical technology are concerned with developments of DDS and TTS. Generally these technologies are formed on the basis of utilization of interactions of drugs with surrounding components such as on a) inter-molecular level; b) particle coating; c) particle-particle interactions d) miscellaneous. The surrounding components thereby include body tissues and organs, and thus a triple interaction among drug, dosage form components and body components should be considered.
We have investigated several topical membrane adhesive dosage forms containing hydroxypropyl cellulose and Carbopol to find such an advanced technology as mentioned above. Here will be described:(1) topical dosage form for carcinoma colli, (2) oral mucosal dosage form for the absorption of insulin, (3) adhesive tablet for aphthous stomatitis, and powder dosage form of nasal absorption of insulin.抄録全体を表示PDF形式でダウンロード (5148K) -
中垣 正幸, 李 殷玉, 山本 いづみ1986 年 106 巻 2 号 p. 110-116
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーThe reaction rate constant k of phospholipase D on L-α-dimyristoyl phosphatidy Icholine (DMPC) liposome with cholesterol was measured by 8-anilino-1-naphthalenesulfonate (ANS) fluorometry. As a result, it has been found that the rate constant was increased by the addition of cholesterol, and that the promoting effect for enzyme reaction by cholesterol increased with an increase in the cholesterol concentration at first, but then decreased after the concentration of maximum promotion.抄録全体を表示PDF形式でダウンロード (947K) -
7β-Amino-3-substituted Methyl-3-cephem-4-carboxylic Acid類の合成貞木 浩, 今泉 弘之, 稲場 太喜広, 平川 龍夫, 室谷 美晴, 才川 勇1986 年 106 巻 2 号 p. 117-122
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーIn order to develop oral cephalosporin having a new substitutent at 3 position, 7β-aminocephalosporanic acid was reacted with various nucleophilic reagents in CF3COOH or sulforan in the presence of BF3.
As a result, 7β-amino-3-substituted methyl-3-cephem-4-carboxylic acids (Ia-w)(substituent: phenyl, thienyl, furyl, sulfonylamino, 1, 1-dioxothiadiazinyl, triazolyl, tetrazolyl, monooxo-or dioxo-diazinyl group) and 3-acylaminomethyl-7β-amino-3-cephem-4-carboxylic acids (IIa-j)(acyl group: alkanoyl, alkenoyl, benzoyl or heterocyclic carbonyl group) were obtained in high yields.抄録全体を表示PDF形式でダウンロード (759K) -
7β-[D (-)-α-Amino-α-(4-hydroxyphenyl) acetamido]-3-substituted Methyl-3-cephem-4-carboxylic Acid類の合成並びに構造-活性相関貞木 浩, 今泉 弘之, 稲場 太喜広, 平川 龍夫, 室谷 美晴, 渡辺 泰雄, 南 新三郎, 才川 勇1986 年 106 巻 2 号 p. 123-128
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリー7β-[D (-)-α-Amino-α-(4-hydroxyphenyl) acetamido]-3-substituted methyl-3-cephcm-4-carboxylic acids (IIa-j) were prepared by the acylation of 7β-amirlo-3-substituted methyl-3-cephem-4-carboxylic acids (substituent: phenyl, furyl, mesylamino, 1, 1-dioxothiadiazinyl, triazolyl, tetrazolyl, monooxo- or dioxo-diazinyl, acetylamino or benzoylamino group) with reactive derivatives of D (-)-α-amino-α-(4-hydroxyphenyl) acetic acid.
The structure-activity relationships of IIa-j indicated that compounds with phenyl group as a substituent were active against Gram positive bacteria, and that compounds with phenyl, 5-carboxy-furan-2-yl or benzoylamino group were active against Gram negative bacterial, but these compounds had weaker antibacterial activity than cephalexin (CEX). And urinary recovery after oral administration of IIa-j into mice was 1-27%, exhibiting lower rate than that of CEX.抄録全体を表示PDF形式でダウンロード (812K) -
7β-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-substituted Methyl-3-cephem-4-carboxylic Acid誘導体の合成並びに構造-活性相関貞木 浩, 今泉 弘之, 稲場 太喜広, 平川 龍夫, 室谷 美晴, 渡辺 泰雄, 南 新三郎, 才川 勇1986 年 106 巻 2 号 p. 129-146
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリー7β-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxyiminoacetamidol]-3-substituted methyl-3-cephem-4-carboxylic acids (IIa-l) were prepared by the acylation of 7β-amino-3-substituted methyl-3-cephem-4-carboxylic acids (substituent: phenyl, 1, 1-dioxothiadiazinyl, monooxoor dioxo-diazinyl, triazolyl, tetrazolyl, acetylamino or benzoylamino group) with reactive derivatives of (Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acid.
IIa-l had a wide antibacterial spectrum against Gram positive and Gram negative bacteria and showed the potent antibacterial activity, being similar to those of cefmenoxime.
For the purpose of developing new oral cephalosporin, various esters (IIIa-1, IVa-m, Va-d) of IIa-l were prepared as one form of prodrugs.
Urinary recoveries of these esters in mice weremeasured. Compounds having 5-methyl-2H-tetrazol-2-yl or 5-chloro-1, 2, 4-triazol-1-yl as a substituent of 3-position and pivaloyloxymethyl or 1-pivaloyloxyethyl as ester group showed high recoveries ranging from 31.2 to 37.3%.抄録全体を表示PDF形式でダウンロード (2290K) -
7-Acylamido-34 [(5-methyl-2H-tetrazol-2-yl) methyl]-3-cephem-4-carboxylic Acid並びに7β-Acylamido-3-[(5-chloro-1, 2, 4-triazol-1-yl) methyl]-3-cephem-4-carboxylic Acid誘導体の合成並びに構造貞木 浩, 今泉 弘之, 稲場 太喜広, 平川 龍夫, 室谷 美晴, 渡辺 泰雄, 南 新三郎, 才川 勇1986 年 106 巻 2 号 p. 147-153
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリー7β-Acylamido-3-[(5-methyl-2H-tetrazol-2-yl) methyl]-3-cephem-4-carboxylic acids and 7β-acylamido-3-[(5-chloro-1, 2, 4-triazol-1-yl) methyl]-3-cephem-4-carboxylic acids (Ia-l) were prepared by the acylation of 7β-amino-3-substituted methyl-3-cephem-4-carboxylic acids with reactive derivatives of acetic acid.
The structure-activity relationships of Ia-l indicated that compounds with 2-(2-aminothiazol-4-yl) acetyl group as acyl group were active against Gram positive bacteria. And compounds with (Z)-2-(2-aminothiazol-4-yl)-2-carboxymethoxyiminoacetyl or (Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetyl group were active against Gram negative bacteria, being active similarly to that of cefmenoxime.
Compounds having the above acyl groups were esterified with pivaloyloxymethyl group to obtain an efficiently absorble esters (VIg-j) through oral administration, whose urinary recoveries in mice were 19.6-37.5%.抄録全体を表示PDF形式でダウンロード (996K) -
メトキシメチレンメルドラム酸とアミノ酸誘導体との反応千葉 卓男, 榊 潤一, 金子 主税1986 年 106 巻 2 号 p. 154-157
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーReaction of 2, 2, -dimethyl-5-methoxymethylene-1, 3-dioxane-4, 6-dione (1) with amino acid esters gave rise to N-(2, 2-dimethyl-4, 6-dioxo-1, 3-dioxan-5-ylidenemethyl) amino acid esters (2) in good yields. Similarly, free amino acids gave N-protected amino acids (3) which were coupled with amino acid esters in the presence of dicyclohexylcarbodiimide afford protected dipeptides. These N-protected amino acids 2a-e and 3a-e, and dipeptides 4a-d, and 5 were examined for antibacterial activity.抄録全体を表示PDF形式でダウンロード (615K) -
吉井 新, 宮本 久美子, 西村 民男1986 年 106 巻 2 号 p. 158-163
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーN-Methyl amidinohydrazones (AH) of substituted benzalacetones were synthesized, and examined in their activities against influenza virus A2/Adachi strain, bacteria and fungi. These AHs exhibited 50% inhibitory concentrations of 4.5-70.5μg/ml and 50% virucidal concentrations of 0.01-2.3μg/ml against the virus in the chorio-allantoic membrane culture. Satisfactory quantitative structure-activity relationships were obtained for inhibitory and virucidal activities against the virus and toxicity to chorio-allantoic membrane.
Almost all AHs showed minimum inhibitory concentrations of 6.25-100μg/mlagainst Mycoplasma gallisepticum and 3.13-100μg/ml against S. aureus, B. subtilis and Pasteurella. Satisfactory quantitative structure-activity relationships were obtained for S. aureus and B. subtilis.抄録全体を表示PDF形式でダウンロード (747K) -
宮原 武恒1986 年 106 巻 2 号 p. 164-168
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーAs metallofluorescent indicators, 2-naphthylamine-N, N-diacetic acid (I), 8-sulfo-2-naphthylamine-N, N-diacetic acid (II), and 7-sulfo-2-naphthylamine-N, N-diacetic acid (III) were studied.
Synthesis and purification of these compounds were easy, comparing with those of N, N, N', N'-tetra (carboxymethyl) dianisidine (Anisidine blue®), and they were stable in an alkaline solution. Acid dissociation constants of ligand [-N (CH2COOH) 2] were determined by potentiometric method. pKa1 (carboxyl) and pKa2 (ammonium) were 2.35 and 5.02 for I, 2.85 and 5.31 for II, 2.69 and 5.06 for III, respectively. Fluorescences of these reagents were quenched by copper (II), cobalt (II), and nickel (II), at pH 4.5-5.5, and copper (II) showed this effect more clearing than the others. Constitution of the copper (II) complexes were 1: 1. Stability constants of these copper (II) complexes which were determined potentiometrically, were 5.8 for II and 5.2 for III logarithmically. Stability constant of complex with I was not determined because ofthe insolubility.
By using these compounds as the indicators, fluorophotometric titration of copper (H)(0.64mg) with 0.01 M ethylenediaminetetraacetic acid (EDTA) yielded good recovery. But those of nickel (II) and cobalt (II) were not available because fluorescence was not shown up by EDTA on nickel (II) and end-point was not clear on cobalt (II).
II is a good indicator in fluorophotometric titration of copper (II) with EDTA, because it is stable in an aqueous solution and has shown stronger fluorescence than I and II.抄録全体を表示PDF形式でダウンロード (606K) -
上能 伊公雄, 中村 敏明, 長谷川 雅哉, 前田 雅子, 小倉 庸蔵, 北澤 式文1986 年 106 巻 2 号 p. 169-175
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーThe accuracy and precision studies and pharmacokinetic analyses for valproic acid (VPA) by using substrate-labeled fluorescent immunoassay (SLFIA method) were performed and the results obtained by SLFIA method were compared with those of gas-liquid chromatography (GLC method). Within- and between-day precision studies of SLFIA method by use of VPA spiked samples in the normal human and rabbit plasma showed a good reproducibilitywith less than 5% as coefficient of variation and there were no significant differences (p>0.05) between the measurements by GLC and SLFIA method. Good correlations between the determinations by GLC (horizontal axis) and SLFIA (vertical axis) method were obtained and the regression equation was y=0.874x+12.4 (n=77, r=0.971, p<0.001) for rabbit samples and y=0.985x+0.866 (n=38, r=0.980, p<0.001) for the samples of patients taking a VPA preparation. These mean values obtained by both of the methods were statistically identical. After a single intravenous bolus injection (VPA dose of 56-71mg/kg) in rabbits, pharmacokinetic parameters were obtained following one-compartment open model. Apparent elimination rate constant by use of SLFIA method was significantly smaller (p<0.001) than that by GLC method, but the volume of distribution by SLFIA method was significantly larger (p<0.05) than that by GLC method. On the other hand, no significant difference was observed (p>0.05) for systemic clearance. These results are reasonably understood that SLFIA method showed significantly higher values which may be due to cross-reaction in lower VPA concentration range (less than 25μg/ml) and moreover suggested significantly lower value which may be caused by the dilution of rabbit plasma samples with a protein-free buffer in higher VPA concentration range (more than 150μg/ml).
These observations showed that SLFIA method was a useful method for clinical measurement of plasma (or serum) VPA level. However, several problems on calculating pharmacokinetic parameters with rabbits with a very short half-life remained to be elucidated.抄録全体を表示PDF形式でダウンロード (1105K) -
金子 英雄, 広田 貞雄1986 年 106 巻 2 号 p. 176-182
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーThe purpose of the present study was to develop the W/O type anti-inflammatory emulsive preparation with the high volume fraction of dispersed phase and high colloidchemical stability.
The dielectric measurement was used to evaluate the degree of particle aggregation of W/O emulsion during preparation or storage. It was found that the values of limiting dielectric constant at low frequency, εl, increased or decreased and parameter of distribution of relaxation frequencies, α, decreased with the rotation time of paddle- and homomixer during preparation. During the storage test, in the case of W/O type emulsive preparation whose surfactant concentration was low, the value of αl became larger with storage time and soon the W/O emulsion separated into two phases. It was considered that the particle aggregation progressed and particle coalescence gave rise to in the W/O emulsive preparation. The W/O emulsion prepared with the sorbitol solution was colloidchemically more stable than with water alone.This stabilizing effect may be due to the orientation of sorbitol molecules onto the interface between dispersed particles and oil phase.抄録全体を表示PDF形式でダウンロード (783K) -
菱実中のHeLa細胞に対する細胞毒性成分について小菅 卓夫, 横田 正実, 杉山 清, 岡本 厚, 斎藤 正志, 山本 藤輔1986 年 106 巻 2 号 p. 183-185
発行日: 1986/02/25
公開日: 2011/01/31
ジャーナル フリーGallic acid was isolated as a cytotoxicconstituent from the fruit of Trapa bispinosa ROXB., by tracing the inhibitory activityagainst HeLa cells.抄録全体を表示PDF形式でダウンロード (317K)
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