著者

太田 和子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.85, no.1, pp.21-27, 1965-01-25 (Released:2010-02-19)

参考文献数

6

---

N-Alkyl (or Aralkyl) derivatives of N-methyl-2-naphthaleneëthylamine (Ia) and N-methyl-2-naphthalenepropylamine (IIa) and their methiodides were synthesized. Tertiary amines (I and II, b-j) obtained and their methiodides were tested for atropine- and papaverine-like activities by the Magnus method, and the relationships between the structures and pharmacological activities were discussed.

著者

太田 和子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.85, no.1, pp.14-20, 1965-01-25 (Released:2010-02-19)

参考文献数

12

被引用文献数

3 5

---

Syntheses of 2-naphthalenealkylamine derivatives, whose carbon number (n) of the alkyl group was varied from n=0-7 and n=10 (IIIa-XIa), and their N, N-dimethyl derivatives (IIIb-XIb) as well as their methiodide (IIIc-XIc) were carried out in order to examine their pharmacological activities.Anti-acetylcholine activities and anti-histamine activities were tested according to the Magnus method. Both activities showed a tendency to strengthen as the carbon number of alkyl group increased. However, the anti-acetylcholine activities of primary amine, whose n is 10, was observed to be a little lower than that of the amine of n=7. As to the anti-histamine activities, dimethylamino derivative of n=2 was found to be the strongest, that of 3 and 4 were weaker and it became stronger as the carbon number increased. The activities of methiodide of n=1 was a little stronger than that of n=2 in both activities.As to the blood pressure activities of primary amines, n=0 showed depression and n=1-4 showed, after a little depression, a rise type, whose degree was observed to be the maximum with n=2 and later weakened to a depress type. Dimethyl compounds were depressive andmethiodide showed usually a continuous rise, after the depression.

著者

木村 郁夫

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.9, pp.867-871, 2014 (Released:2016-09-17)

参考文献数

27

---

創薬ターゲットの大半を占めるGタンパク質共役型受容体(G protein-coupled receptor:GPCR)はこれまで広く注目されてきた.その中でも特に,その重要な生理機能から脂肪酸受容体の研究は,近年大きく進展している.例えば最近,この脂肪酸受容体のうちのGPR120がヒトの肥満の原因遺伝子であり,その一塩基変異が肥満と密接に結びつくことが明らかになっている.このことを含め,現在,機能解析が行われている各種脂肪酸受容体について,我々の研究成果を含めた最近の知見と糖尿病や肥満などに代表される生活習慣病の創薬ターゲットとしての展望も含めて概説する.

著者

渡辺 俊典

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.47, no.1, pp.17-20, 2011-01-01 (Released:2017-02-11)

著者

井原 賢 張 晗 花本 征也 田中 宏明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.3, pp.281-287, 2018 (Released:2018-03-01)

参考文献数

16

---

Pharmaceuticals are widely found in aquatic environments worldwide. Concern about their potential risks to aquatic species has been raised because they are designed to be biologically active. To address this concern, we must know whether biological activity of pharmaceuticals can be detected in waters. Nearly half of all marketed pharmaceuticals act by binding to the G protein-coupled receptor (GPCR). In this study, we measured the physiological activity of GPCR-acting pharmaceuticals in effluent from a wastewater treatment plant (WWTP) and upstream and downstream of its outfall in Japan during 2 years. We used the in vitro transforming growth factor-α (TGFα) shedding assay, which accurately and sensitively detects GPCR activation, to investigate the antagonistic activities of water extracts against receptors for dopamine (D2) and histamine (H1). Activities detected in waters were quantified as antagonist equivalent quantities (EQs). In WWTP effluent extracts, antagonistic activity was detected at several hundred ng/L of sulpiride-EQ (D2) and several μg/L of diphenhydramine (DIP)-EQ (H1). In downstream river water extracts, antagonistic activity against H1 was around several hundred ng/L of DIP-EQ, higher than that upstream owing to the WWTP effluent. This review discusses the research needed to resolve the concern about potential risks of pharmaceuticals in waters to aquatic species.

著者

武田 豊彦 鈴木 裕介 稲津 邦平 坂元 照男 前川 秀幸

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.109, no.6, pp.395-401, 1989-06-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

2 6

---

Cephalothine sodium (CET-Na) in crystals can be obtained by freezing the aqueous solution and subsequent warming at a fixed temperature for facilitating crystallization prior to vacuum application for drying. The product has, however, been found to unavoidably contain traces of the amorphous CET-Na, which causes a rapid color development during storage. By using thermal analysis, differential scanning calorimetry (DSC), electric conductometry, and polarized light cryomicrographic techniques, the solubilities in water, freezing point, eutectic point, and melting behavior of CET-Na in aqueous solution were investigated. The investigation demonstrated that CET-Na in supersaturated aqueous solution is very stable, and that seeding with microcrystalline CET-Na to the supersaturated solution and subsequent cooling of the mixture till its freezing point gives neither any evidence for crystallization nor for growth of the seed crystals. The freeze-drying of CET-Na in the supersaturated solution after seeding has been demonstrated to give crystalline CET-Na contaning neither of amorphous nor of quasicrystalline form.

著者

芦澤 一英 内川 清彦 服部 禎一 石橋 泰雄 三宅 康夫 里 忠

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.110, no.3, pp.202-209, 1990-03-25 (Released:2008-05-30)

参考文献数

34

---

An X-ray diffraction methods and Fourier transform infrared analysis with photoacoustic detector (FTIR-PAS) for estimation of the degree of crystallinity of crystalline E1040 formulation was established. The X-ray procedure to determine the crystallinity of E1040 was based upon the measurement of the total scattering and the scattering from the crystalline region of the drug. The FTIR-PAS procedures are based upon the measurement of the peak height ratio at 1628 cm-1 and measurement of the spectral region between 2400 and 3700 cm-1 by the Partial least squares (PLS) techniques. The data of the degree of crystallinity from the X-ray diffraction methods are consistent with the data from FTIR-PAS methods. The increase of the degree of crystallinity of the drug formulation decreased the decomposition rate of E1040. As a result, it had become apparent that two analytical procedures were actually valid. This assured optimizing process conditions which affect the improvement of crystallinity.

著者

鈴木 裕介 武田 豊彦 稲津 邦平 坂元 照男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.110, no.11, pp.858-868, 1990-11-25 (Released:2008-05-30)

参考文献数

7

---

Seeding and subsequent freeze-drying of aqueous cephalothin sodium (CET-Na) solution of supersaturated concentrations, which preliminarily received an excess of mechanical stress, have been reported to make the product unacceptable in pharmaceutical elegance and in chemical stability upon storage. In order to find out the cause, the CET-Na solution that preliminarily received mechanical stress has been examined as to its crystallization behavior during freezedrying process, by using polarizedlight cryomicroscopy, scanning electron microscopy, cryodifferential scanning calorimetry, refractometry, viscositometry, and surface tensiometry. Aqueous CET-Na solution of supersaturated concentrations, to which an excess of mechanical stress was given, has been demonstrated to exhibit the following features : in the process of seeding and subsequent freeze-drying, the solution shows an incomplete crystallization at -40°C ; in the crystal growth stage at -5°C, crystals are found to be difficult to grow sufficiently from the seeds as their nuclei. These findings indicate that the supersaturated solution has changed to an unusual state upon receiving such stress, the state being different from the state of untreated solution in that the solution thus treated shows physico-chemical properties capable of easy crystallization through a simple step of freezing. The change as such in physico-chemical properties has also been estimated to have resulted from a structural change of associated molecules of CET-Na in its supersaturated solution into a condensed state quite similarly to that of liquid crystals.

著者

鈴木 裕介 武田 豊彦 稲津 邦平 坂元 照男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.110, no.11, pp.849-857, 1990-11-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

1 2

---

A method of seeding and subsequent freeze-drying of aqueous cephalothin sodium (CET-Na) of supersaturated concentrations was employed in an experiment with a regular production scale. The freeze-dried plugs of non-uniformity in appearance were consequently obtained together with those of white in color and in high uniformity in appearance. Such plugs of irregular shape have been found to show a marked color development during storage, and the reconstitution time was also prolonged. Scanning electron microscopy, powder X-ray diffractometry, and thermogravimetry have all demonstrated that the plugs of irregular appearance show dense aggregates of fine crystals of a high non-crystallinity by an incomplete crystal growth. Investigation has then been made with supersaturated CET-Na solution, which has preliminarily received varying mechanical stresses in varying time courses of temperature, similarly to a regular production program, for the purpouse of achieving the reproducibility of such unacceptable plugs. It has been demonstrated that by a more prolonged storage at a lower temperature of CET-Na in supersaturated solution the plug may surely contain aggregates of more fine crystallites of a higher non-crystallinity, accordingly have a higher irregularity in appearance and exhibit a more marked deterioration in pharmaceutical qualities.

著者

井上 正義 島 和弘 稲津 邦平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.104, no.9, pp.973-980, 1984-09-25 (Released:2008-05-30)

参考文献数

14

---

Investigation has been made to obtain the crystallinity of cephalothin sodium in seeded and frozen aqueous solution from electrical conductivity (conductivity), with a result that crystallinity (αt) can be given by the equation of αt=λT-λt/λT, where λT is the initial conductivity and λt stands for the conductivity obtained after t hours. Observed values of crystallinity by the conductivity method are in good agreement with crystallinity data by infrared method and X-ray diffraction method of the freeze-dried material. Further investigation has been made to find out whether it is possible to apply the no-seeding conductivity method for the crystallinity of dicethiamin hydrochloride in solution capable of spontaneous nucleation and transformation to its crystalline state. The result has consequently demonstrated that, in some cases of no-seeding, the phase transition is not uniform, or otherwise, the conductivity change provides an incomplete indication of nucleation and growth of perfect crystals. From the above, it may as well be said to be safe to set a limit to a seeded system, when the authors' conductivity method is applied for obtaining the crystallinity of a drug in frozen solution.

著者

井上 正義 田中 廣義 島 和弘 稲津 邦平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.105, no.3, pp.289-295, 1985-03-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

1 1

---

The effect of organic solvent on the growth rate of cephalothin sodium (KF) after seeding in frozen solution was investigated. All of used solvents accelerated crystal growth of KF and it was found that the accelerative effect of solvent increased with an increase in dielectric constant of solvent. KF formed micelle in aqueous solution and the solvent lower the freezing temperature of the micelle and it can be assumed that the lowering of the freezing temperature of the micelle related to the volume of solvent existing in the micelle. Alcohol lower larger the freezing temperature of the micelle than ketone and nitrile, but the accelerative effect of alcohol on the growth rate was less than that of ketone and nitrile. The effect of the concentration of ethanol and acetone was investigated and it seemed that ethanol accelerated nucleation. Nevertheless, the accelerative effect of ethanol on the growth rate was less than that of acetone. These results suggested that simultaneous use of solvent having a different mode of action is effective for crystallization of KF in frozen solution by spontaneous nucleation.

著者

井上 正義 島 和弘 稲津 邦平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.104, no.12, pp.1268-1274, 1984-12-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

3 2

---

The growth rate of cephalothin sodium (KF) after seeding in frozen solution was measured. Crystal growth of KF followed equation (1) untill α=0.98. 1-(1-α)1/3=(1/3N) (Kt)N……(1) where α is crystallinity, K is rate constant, t is time, and N is parameter depending on the freezing temperature and the amount of seed. Crystal growth of KF in the frozen solution hardly changed when the concentration of KF was in the range of 19.4% to 28.6% but it was remarkably dependent on the amount of seed at the constant freezing temperature. According to the decrease in the amount of seed at the constant freezing temperature, the value of N increased and the rate constant (K) decreased. The growth rate increased with a rise of freezing temperature, and had the maximum value at a temperature little below the eutectic temperature. The activation energy of crystal growth of KF in the range of -5°C to -14°C was 49 kcal/mol.

著者

鈴木 裕介 武田 豊彦 稲津 邦平 坂元 照男 前川 秀幸

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.109, no.6, pp.388-394, 1989-06-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

1 1

---

Cephalothin sodium (CET-Na) prepared according to the conventional freeze-drying methods is known to easily develop color during storage. Since amorphous CET-Na has been reported to be markedly unstable, the color development is thought to be due to the presence of traces of CET-Na in an amorphous state observed with scanning electron microscopy. Quantitation by use of the powder X-ray diffractometry of such traces of amorphous CET-Na has proved to be of little use. Thermogravimetry (TG) and differential scanning calorimetry (DSC) have demonstrated that the freeze-dried CET-Na by the conventional methods contains three types of CET-Na : amorphous (unstable phase), quasi-crystalline (metastable phase). Pyrolysis initiation temperatures of these three types of CET-Na have been demonstrated to become higher in this order. A new parameter for the evaluation of non-crystallinity of CET-Na has been introduced, in which the ratio is calculated from the data of the total weight loss observed through the pyrolysis of both amorphous and quasi-crystalline CET-Na against the total weight loss of all components during the pyrolysis of sample specimen. The ratio thus calculated is defined as "non-crystallinity". This new parameter has successfully been introduced to establish a good correlation to the degree of increasing color intensity with aging of freeze-dried CET-Na.

著者

松浦 巌 清家 康子 川真田 正信

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.103, no.1, pp.85-93, 1983-01-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

1 1

---

Kinetic analysis of thermal decomposition was carried out using thermogravimetry (TG) and differential scanning calorimetry (DSC). The linear equations of n order, phase-boundary, nucleation growth and diffusion-controlled reaction under linear heating conditions were derived for the estimation of the rate constant and the activation energy. The method to determine the reaction mechanism was shown by evaluation of linearity. The equations were applied to the TG and DSC curves of dehydration of calcium oxalate monohydrate and elimination of carbon monoxide from calcium oxalate. The dehydration was fit to two-dimensional phase-boundary reaction and the activation energy was calculated as 85 kJ/mol. But the dehydration at a high-speed heating rate proceeded as apparent three-dimensional diffusion-controlled reaction. The elimination of carbon monoxide from calcium oxalate was fit to phase-boundary reaction and the activation energy was calculated as 196 kJ/mol for three-dimensional phase-boundary reaction and 182 kJ/mol for two-dimensional phase-boundary reaction.

著者

山口 寿 川真田 正信 仲井 由宣 山本 恵司

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.102, no.5, pp.463-468, 1982-05-25 (Released:2008-05-30)

参考文献数

8

被引用文献数

1 1

---

By use of X-ray diffractometry, thermal analysis and infrared spectroscopy, the crystal forms of N-(2, 6-dimethylphenyl)-Δ8-dihydroabietamide were investigated. Two polymorphic forms (form I and II), two solvates (cyclohexane and CCl4), and an amorphous form were identified. Heating of form II induced a solid transformation to form I. The transition of form I and II to the amorphous form was observed by grinding. Each solvate contained 9.0% cyclohexane and 16.0% CCl4 respectively, i.e., drug : solvent=2 : 1. The activation energy of the desolvation was determined from TG curves by using Ozawa's method, and calculated as 72.2 kcal/mol for the cyclohexar solvente, and 35.5 kcal/mol for the CCl4 solvate.

著者

太田 彦人 瀬戸 康雄 角田 紀子

出版者

公益社団法人 日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.39, no.2, pp.155-160, 1993

被引用文献数

2

---

The determination and confirmation of trans-10-hydroxydecenoic acid (10-HDA) in royal jelly (RJ) were developed by capillary gas chromatography (GC) and GC-chemical ionization mass spectrometry (CI-MS) equipped with an ion trap detector (ITD) as a mass spectrometer. It was found that 10-HDA extracted with dichloromethane at pH 2.5 was converted into trimethylsilyl (TMS) derivative in a constant yield by the reaction with N, O-bis (trimethylsilyl) acetamide at room temperature for 15 min. The recovery of 10-HDA (50 μg) was 99.5%. The TMS derivatives of raw RJ tested showed a satisfactory result of separation and sensitivity by GC using a DB-1 capillary column with a flame ionization detector. The linear dynamic detection range was approximately from 50 ng to 500 μg (16.7-167000 ppm) determined using n-eicosane as an internal standard. The minimum detectable amount of 10-HDA was found to be 50 ng (16.7 ppm) at the split ratio of 40 : 1 of the split injection. The amount of 10-HDA in the raw RJ sample was 2.28±0.04% determined by the GC method and 2.25±0.01% by the HPLC method as described previously, respectively. The TMS derivatives of 10-HDA and its related compounds in the raw RJ were confirmed by ITD-GC. The diagnostic ions of TMS-HDA were presented at m/z 331 (M+1), 315 (M-Me), and 241 (M-OTMS) in isobutane CI mode. The present GC method is an easier and more convenient method for the analysis of 10-HDA in RJ and is applicable for the determination and confirmation of 10-HDA in forensic and food samples.

著者

澤田 康文 佐藤 宏樹

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.48, no.11, pp.1062-1066, 2012-11-01 (Released:2016-12-16)

著者

Kimura Masahiro Shindo Mitsuno Moriizumi Toshiyuki Tagawa Noriko Fujinami Aya Kato Ikuo Uchida Yoshiki

出版者

公益社団法人 日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.62, no.6, pp.586-590, 2014

被引用文献数

6

---

Salusin-β has been detected in numerous mammalian tissues and has been shown to have various effects on the cardiovascular system. In this study, we showed that salusin-β exhibited potent antibacterial activity against Gram-positive microorganisms such as Bacillus subtilis NBRC 3513, Bacillus megaterium ATCC 19213, Staphylococcus aureus NBRC 12732, and Staphylococcus epidermidis NBRC 12933. A cytoplasmic membrane-depolarizing assay using the DiSC3(5) dye revealed that the addition of 4 nmol/mL of salusin-β caused the leakage of fluorescence dye from Staphylococcus aureus NBRC 12732. The antimicrobial potency and circular dichroism (CD) spectroscopy of five analogs related to salusin-β were examined to determine structure-function relationships in its N- and C-terminal regions. The results obtained suggest that the N-terminal sequences of the salusin-β molecule are important for the expression of the potent antimicrobial activity of this peptide. A profile corresponding to that of the α-helix conformation was observed in the salusin-β solution.

著者

勝見 英正 草森 浩輔 坂根 稔康 山本 昌

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.9, pp.1129-1133, 2010 (Released:2010-09-01)

参考文献数

19

被引用文献数

7 6

---

Bisphosphonates are carbon-substituted pyrophosphate (PCP) analogues that exhibit high affinity to hydroxylapatite and inhibit bone resorption after their administration. They are widely used as the first-choice drug for the treatment and prevention of bone diseases, including Paget's disease, hypercalcemia of malignancy, and osteoporosis. However, the oral bioavailability of bisphosphonates is quite low (1-2%). In addition, the oral administration of bisphosphonates has been associated with mucosal damage, including gastritis, gastric ulcer, and erosive esophagitis. Therefore, it is highly desirable to develop new delivery systems that improve their bioavailability and safety. In this review, recent challenges in the developments of novel delivery system of bisphosphonates are summarized. Then, future developments of delivery system of bisphosphonates are also discussed in order to improve their therapeutic efficacy and safety in the treatment of bone diseases.

著者

畠山 大

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.2, pp.205-214, 2017 (Released:2017-02-01)

参考文献数

40

---

The PA, PB1, and PB2 subunits, components of the RNA-dependent RNA polymerase of influenza A virus, and the nucleoprotein (NP) interact with the genomic RNA of influenza viruses and form ribonucleoproteins. Especially, the PB2 subunit binds to the host RNA cap [7-methylguanosine triphosphate (m7GTP)] and supports the endonuclease activity of PA to “snatch” the cap from host pre-mRNAs. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is necessary for interaction with acetyl-CoA found in eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that the recombinant PB2 cap-binding domain that includes the VRG site interacts with acetyl-CoA; moreover, it was found that this interaction could be blocked by CoA and various HAT inhibitors. Interestingly, m7GTP also inhibited this interaction, suggesting that the same active pocket is capable of interacting with acetyl-CoA and m7GTP. To elucidate the importance of the VRG site on PB2 function and viral replication, we constructed a PB2 recombinant protein and recombinant viruses including several patterns of amino acid mutations in the VRG site. Substitutions of 2 or 3 amino acid residues of the VRG site to alanine significantly reduced PB2's binding ability to acetyl-CoA and its RNA polymerase activity. Recombinant viruses containing the same mutations could not be replicated in cultured cells. These results indicate that the PB2 VRG sequence is a functional site that is essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication. I will also discuss some novel functions of NP in this review.