著者

Tomoko Otsuka Yosuke Kuroiwa Kazunari Sato Kazunari Yamashita Tadashi Hakomori Shin-ichiro Kimura Yasunori Iwao Shigeru Itai

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.5, pp.554-561, 2018-05-01 (Released:2018-05-01)

参考文献数

24

被引用文献数

6

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The properties of wet mass, which indicate the progress of high shear granulation processes, usually have an effect on final product properties, such as tablet dissolution. The mixer torque rheometer (MTR) is a useful tool for quantitatively measuring the ‘kneading state’ of wet mass and detecting differences in granules. However, there have been no studies of the relationship between the MTR torque and the final product properties to date. In this study, we measured the MTR torque of wet granules at different kneading states, which were prepared by changing the granulation conditions. We then evaluated the relationship between the MTR torque and the dissolution rate of the final product properties. The amperage of the high shear granulator is usually monitored during granulation, but we could not detect a difference in the kneading state through the amperage. However, using MTR torque we were able to quantify the difference of the wet mass. Moreover, MTR torque showed a high correlation with dissolution, compared with the correlations with other intermediate properties, such as granules particle size and tablet hardness. These other properties are affected by following processes and are not properties that directly relate to the kneading state. Thus, MTR torque is a property of wet mass after granulation, and it can be used to directly evaluate differences of the kneading state, and as a result, dissolution. These results indicate the importance of controlling the kneading state, i.e., the progress of granulation, and the utility of MTR for detecting differences in wet mass.

著者

井口 貞彦 岩村 浩幸 西崎 稔 林 昭夫 瀬の口 和彦 小林 馨 坂木 克人 蜂谷 勝敏 市岡 由美子 川村 雅範

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.6, pp.1462-1469, 1992-06-25 (Released:2008-03-31)

参考文献数

12

被引用文献数

115 152

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A novel, highly cardioselective ultra short-acting β-blocker, ONO-1101, has been developed for application in the emergency treatment of tachycardia and better control of heart rate in surgery. This agent is approximately nine times more potent in β-blocking activity in vivo and eight times more cardioselective in vitro than esmolol. This β-blocking drug has a short duration of activity, enabling rapid recovery after cessation of administration if side effects occur. It can be used safely in patients suffering from acute heart disease and represents a major therapeutic advance in the treatment of heart disease.

著者

Kozo ODA Akira YOSHIDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.46, no.6, pp.893-899, 1998-06-15 (Released:2008-03-31)

参考文献数

18

被引用文献数

1 1

---

The C-2 side-chain substitution reaction of a sulfoxide and a sulfone derived from a p-nitrobenzyl (1R, 5S, 6S)-6-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-[2-(diethylcarbamoyl)phenylthio]-1-methylcarbapen-2-em-3-carboxylate with various mercaptans progressed smoothly in the presence of magnesium bromide. Bromomagnesium thiolate prepared from mercaptans proved to be especially effective for the substitution reaction and gave precursors of 1β-methylcarbapenem antibiotics in high yield.

著者

Kozo ODA Akira YOSHIDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.45, no.9, pp.1439-1446, 1997-09-15 (Released:2008-03-31)

参考文献数

14

被引用文献数

3 5

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S-[2-(Dialkylaminocarbonyl)phenyl](2R)-2-[(3S, 4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxo-4-azetidinyl]thiopropionate (11), useful intermediates for the synthesis of 1β-methylcarbapenems including 1β-methylthienamycin, were prepared in a highly stereoselective manner by the reaction of E-1-(tert-butyldimethylsilyloxy)-1-[2-(dialkylaminocarbonyl)phenylthio]-1-propene (10) with commerically available (3S, 4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-acetoxyazetidin-2-one (6) in the presence of zinc chloride catalyst. The diethylaminocarbonyl derivative (11b) was particularly convenient for practical production because of its highly crystalline nature.

著者

Seif-Eldin Nasr Ayyad Khalid Omar Al-Footy Walied Mohamed Alarif Tariq Rashad Sobahi Salim Ahmed Bassaif Mohamed Saleh Makki Abdullah Mohamed Asiri Amani Yahya Al Halawani Adel Farid Badria Farid Abd Al-raheem Badria

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.59, no.10, pp.1294-1298, 2011-10-01 (Released:2011-10-01)

参考文献数

16

被引用文献数

17 38

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The petroleum ether extract of the red alga Laurencia obtusa afforded three new C15 acetogenins (cyclic ether enyne): (12Z)-cis-maneonene-D (1), (12E)-cis-maneonene-E (2), and (12Z)-trans-maneonene-C (3), along with one known cis-maneonene-A (4). Blood neutrophils were prepared, cultured, and incubated for 24, 48, and 72 h in medium with and without isolated compounds. Blood neutrophils were prepared, cultured, and incubated for 24, 48 and 72 h in medium with and without the isolated compounds. Both morphology and DNA fragmentation methods assessed the percentage of neutrophils apoptosis in each culture. In the present study, several observations have been made concerning the apoptosis-inducing or inhibiting effect of 1 and 2. Both compounds had no inhibition of apoptosis but apoptosis was enhanced significantly by aging. However, 1 stimulated apoptosis of normal only at the initial 24 h. After that there was no significant difference in apoptosis with or without compound 1, while 2 stimulated apoptosis at all the times. The apoptosis induced by these two compounds was demonstrated by DNA fragmentation assay and microscopic observation. These observations suggest that compounds 1 and 2 may be involved in regulation of programmed death in the initiation and propagation of inflammatory responses.

著者

大塚 誠 松本 崇弘 金庭 延慶

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.4, pp.1784-1793, 1986-04-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

70 95

---

The effect of grinding in an agate centrifugal ball mill at 200 rpm on the physicochemical properties of indomethacin (IMC) polymorphs was studied by means of X-ray diffraction analysis, infrared spectroscopy and differential scanning calorimetry. The α and γ forms (metastable and stable forms) of IMC were ground at 4°C ant at 30±0.5°C, and the degree of crystallinity (Xc) of the ground products was measured by the X-ray diffractional internal standard method.The Xc of the γ form ground at 4°C decreased with increasing grinding time, and was 0% after 4 h, that is, the γ form had been converted to a noncrystalline solid. After grinding for 1 h at 30°C, about 45% of γ form of IMC was converted to noncrystalline solid, while the product ground for 10 h was transformed to the α form.The Xc of the α form ground for 2 h at 4°C was 0%, that is, the αform had been converted to a noncrystalline solid within 2 h at 4°C. The Xc of the α form ground at 30°C decreased with increasing grinding time and the value after 10 h was about 60%.The solubility in distilled water at 35°C of the γ form ground for 10 h at 4°C was about 60% larger than that of the intact γ form. The solubilities of the γ form gournd for 10 h at 30°C, the α form gound for 10 h at 4°C and the α form gound for 10 h at 30°C were all the same, 0.94 mg/100 ml, which is equal to that of the α form at 35°C.

著者

大塚 誠 金庭 延慶

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.32, no.3, pp.1071-1079, 1984-03-25 (Released:2008-03-31)

参考文献数

9

被引用文献数

35 43

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The effects of grinding on the physicochemical properties of cephalexin (CEX) were studied by means of water content measurements, differential thermal analysis (DTA), differential scanning calorimetry (DSC), X-ray diffraction analysis and scanning electron microscopy (SEM). The water content of CEX which had been ground for 4h and converted to a noncrystalline state was proportional to relative humidity (RH) in the range of 0-62% RH, and was about 2 mol/mol at 62-82% RH. The water content of intact crystal phase IV was about 1 mol/mol at 20-75% RH, and about 2 mol/mol at 82-95% RH. The X-ray diffraction data indicated that ground CEX remains in the noncrystalline state until it has absorbed more than about 2 mol of water per mol. At 62% RH, the water content of phase IV increased with increasing grinding time due to the conversion to noncrystalline state. The dehydration point of the ground CEX was depressed by up to about 25°C with increasing grinding time, and the decomposition point of the ground products was depressed by up to about 30°C. In general, the physicochemical properties changed rapidly when the crystallinity of the ground product fell below about 25%. The activation energy and mechanism of dehydration were determined by using nonisothermal kinetic analysis (Criado's method). The dehydration of the product ground for 4h (noncrystalline solid) followed first-order kinetics and its activation energy and latent heat were calculated to be 14.83 kcal/mol and 8.31 kcal/mol, respectively. The product ground for 4h was about 2.5 times more soluble than intact phase IV. The dehydration behavior and solubility of the product ground for 4h were different from those of the freeze-dried product, even though both products are in a noncrystalline state.

著者

金庭 延慶 大塚 誠

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.4, pp.1660-1668, 1985-04-25 (Released:2008-03-31)

参考文献数

7

被引用文献数

40 53

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The effect of grinding in an agate centrifugal ball mill on the transformations of polymorphs of chloramphenicol palmitate (CPP) were studied by means of X-ray diffraction analysis, infrared (IR) spectroscopy and differential scanning calorimetry (DSC). Three kinds of the polymorphs of CPP were reported, that is, forms A, B and C. There was no change in the X-ray diffraction profile of form A (stable form) on grinding for 600 min, but its profile became broader than that of intact form A. There was no change in the X-ray diffraction profile of form B (meta-stable form) on grinding for 130 min, but form B was transformed into form A by grinding for more than 140 min. Form B ground for 140 min contained about 35% form A ; when ground for 150 min, it contained about 80% form A, and when ground for more than 150 min, it contained a constant level of about 80% form A. The X-ray diffraction profile of form C (meta-stable form) suggested that form C was transformed into form B by grinding for 20 min ; thereafter the product was transformed into form A by grinding for 160 min. Form C ground for 4 min contained about 60% form B ; when ground for 20 min, it contained about 100% form B, and ground for 160 min, it contained about 80% form A. These results suggest that the transformations of polymorphs of CPP by grinding are form C→form B→form A. The melting point (mp) and the heat of fusion (H) were measured by DSC. The mp and the H of form A obtained by grinding were about 2.5°C and about 2.5 kcal/mol lower than those of intact form A, respectively, and the solubility in 50% (v/v) aqueous isopropyl alchohol was about twice that of intact form A.

著者

Tatsuya Hirano Tomohiko Kinoshita Daichi Kazamori Satoshi Inoue Kouji Nishimura Asuka Sakurai Kensuke Ohishi Yasuhiro Kuramoto Hirotaka Amano Akira Yazaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.3, pp.235-238, 2018-03-01 (Released:2018-03-01)

参考文献数

25

被引用文献数

5

---

WFQ-101 with a unique N-1 substituent, 5-amino-4-fluoro-2-(hydroxymethyl)phenyl group, was selected as a lead compound through combination screening based on antimicrobial activity and the efflux index against quinolone-resistant (QR) Pseudomonas aeruginosa (P. aeruginosa). Through structural optimization, we identified WFQ-228 as a novel fluoroquinolone antibiotic candidate. WFQ-228 had potent and superior activity in comparison to levofloxacin (LVX) and ciprofloxacin (CIP) against clinical isolates of P. aeruginosa, Escherichia coli and Acinetobacter baumannii, including QR strains. Furthermore, WFQ-228 demonstrated the potential to overcome major mechanisms of drug resistance; its antimicrobial activity was less affected by both pump-mediated efflux and mutations of the quinolone resistance-determining region in P. aeruginosa compared with LVX and CIP. These results suggest that WFQ-228 is a promising candidate for further evaluation in the treatment of infections caused by QR Gram-negative pathogens.

著者

Masaki Takigawa Hirofumi Masutomi Yuki Kishimoto Yoshitomo Shimazaki Yoshitomo Hamano Yoshitaka Kondo Tomio Arai Jaewon Lee Toshihiro Ishii Yoshiko Mori Akihito Ishigami

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.7, pp.975-983, 2017-07-01 (Released:2017-07-01)

参考文献数

21

被引用文献数

1 8

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Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used against methicillin-resistant, Gram-positive cocci despite the nephrotoxic side effects. VCM-induced nephrotoxicity has been reported in 5–28% of recipient patients. Therefore, renal failure induced by VCM has become an important clinical problem. However, the exceedingly complex mechanism of VCM-induced nephrotoxicity is not fully understood. Therefore, this study was designed to clarify time-dependent alterations of VCM-induced nephrotoxicity in mice as a step toward decreasing the risks of kidney injury associated with VCM therapy. VCM was injected intraperitoneally into mice at a dose of 400 mg/kg body weight at 24-h intervals for 3, 5, 7, and 14 d. At 24 h after the last injection, we examined histopathological alterations of the kidney as well as blood biochemistry. VCM administration resulted in a decrease of body weight and increase of kidney weight. Histological examination revealed renal damage such as dilated proximal tubules with occasional casts and interstitial fibrosis in VCM-treated mice. Furthermore, immunohistochemical staining with anti-CD10 and anti-single-stranded DNA antibodies highlighted damaged renal proximal tubules with marked dilatation as well as numerous apoptotic cells as early as day 4 of VCM-treatment. The severity of symptoms progressed until day 15. These results suggest that VCM-induced renal damage and incipient renal failure begin soon after the start of treatment and progressively worsen. This is the first report describing the time-dependence of VCM-induced nephrotoxicity in mice and depicting a model that clarifies the mechanisms of this tissue damage.

著者

Taishi Higashi Daisuke Iohara Keiichi Motoyama Hidetoshi Arima

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.3, pp.207-216, 2018-03-01 (Released:2018-03-01)

参考文献数

174

被引用文献数

40

---

Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed “supramolecular pharmaceutical sciences,” which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.

著者

小島 孝一 雨宮 茂雄 末宗 洋 酒井 浄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.7, pp.2750-2761, 1985-07-25 (Released:2008-03-31)

参考文献数

7

被引用文献数

3 4

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A general method for the stereospecific synthesis of 2, 3-trans-3, 4-cis-trisubstituted cyclopentanones (9) is described. This synthetic method has the advantage that three functional groups can be stereospecifically introduced on a five-membered ring by the catalytic hydrogenation of 2, 3, 4-trisubstituted cyclopentenones. Furthermore, 9 could be stereospecifically converted to 1, 2-trans-2, 3-trans-3, 4-cis-trisubstituted cyclopentanols (20) and 3, 4-cis-disubstituted cyclopentanones (11) by a simple procedure. These synthetic methods may be useful for the synthesis of natural products containing a five-membered ring.

著者

浜名 政和 山崎 企善

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.11, no.4, pp.411-414, 1963-04-25 (Released:2008-03-31)

被引用文献数

6 11

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While quinoline 1-oxide itself is not capable to react with acetyl cyanide, an exothermic reaction occurred in the presence of acetic anhydride, and quinaldonitrile and 2-quinolinepyruvonitrile were obtained. The former was a sole product from the reaction in dioxane or chloroform, whereas the latter was the main product without solvent.

著者

後藤 良宣 山崎 企善 浜名 政和

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.19, no.10, pp.2050-2057, 1971-10-25 (Released:2008-03-31)

被引用文献数

15 23

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Six kinds of 2-aryloxazole N-oxide derivatives were prepared, and their reactions with phosphoryl chloride and acetic anhydride were studied. Methyl group located on the 4-position of 2-aryloxazole N-oxide was easily subjective to nucleophilic attack as an active methyl group in the reaction with phosphoryl chloride or acetic anhydride, whereas 5-methyl group was inert to such an attack.

著者

浜名 政和 舟越 和久 執行 洋陸 口野 嘉幸

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.2, pp.346-350, 1975-02-25 (Released:2008-03-31)

被引用文献数

4 13

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The 1, 3-dipolar cycloaddition between quinoline N-oxide (I) and methyl propiolate progressed in the presence of acetic anhydride or hydroquinone to afford methyl α-formyl-2-quinolineacetate (IIa). The reaction with ethyl propiolate in the presence of hydroquinone gave the corresponding ethyl ester (IIb). The reaction of I with methacrylonitrile in the presence of hydroquinone produced cyanohydrin of 2-acetonylquinoline (VIII) or 2-acetonylquinoline (IX) and 2-cyanoquinoline (X). Isoquinoline N-oxide (XI) was less reactive and resisted the reaction with propiolates, but reacted with methacrylonitrile in the presence of hydroquinone to give 1-acetonyl-isoquinoline (XII), 1-cyanoisoquinoline (XIII) and isoquinoline.

著者

浜名 政和 山崎 企善

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.10, no.1, pp.51-54, 1962-01-25 (Released:2008-03-31)

被引用文献数

7 11

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Alkaline ferricyanide oxidation of some aromatic N-oxides was examined. Quinoline 1-oxide, lepidine 1-oxide, and isoquinoline 2-oxide were smoothly oxidized to the corresponding N-hydroxy-carbostyrils or-isocarbostyrils. From quinaldine 1-oxide, only a small amount of quinaldinic acid 1-oxide was obtained. In contrast, pyridine and nicotinic acid 1-oxide were not affected by this oxidation procedure.

著者

浜名 政和 山崎 企善

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.11, no.4, pp.415-421, 1963-04-25 (Released:2008-03-31)

被引用文献数

21 31

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Quinoline 1-oxides were found to react smoothly with compounds containing reactive hydrogens in the presence of acetic anhydride, producing the corresponding 2-substituted quinolines. The yields were generally good to excellent in the reactions of ethyl cyanoacetate, 1, 3-indandione, diethyl malonate, diethyl nitromalonate, ethyl nitroacetate (e. g. ethyl α-cyano-2-quinolineacetate in 88% yield), but acetone, acetophenone or phenylacetonitrile could not enter into the reaction. The reaction of quinoline 1-oxide using benzoyl chloride instead of acetic anhydride and those of pyridine 1-oxides in the presence of acetic anhydride proceeded similarly but in much lower yields.

著者

浜道 則光 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.12, pp.3253-3256, 1990-12-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

1 3

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Substituent and solvent effects on the tautomeric equilibration (E/Z) of α-(N-alkyl and -arylaminomethylene)-9-(methoxymethyl)-9H-purine-6-acetonitriles (3a-q) have been studied by means of proton nuclear magnetic resonance spectroscopy in protic and aprotic solvents at 25°C. In chloroform-d these compounda (3a-q) exist mainly as the E-form. On the other hand, in methanol-d4 or dimethylsulfoxide-d6 the alkylamines (3a-c), phenylamine (3e), meta- or para-substituted phenylamines (3f-j) and 2, 6-disubstituted phenylamines (3p and q) exist mainly as the Z-form, while the trityl compound (3d), and ortho-substituted compounds (3k-o) showed a predominance of the E-form.

著者

浜道 則光 宮坂 貞

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.7, pp.2018-2019, 1990-07-25 (Released:2008-03-31)

参考文献数

7

被引用文献数

1 1

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6-Dicyanomethylene-9-tetrahydrofuranylpurine (4), which was obtained by the reaction of 9H-1, 6-dihydropurine-Δ6, α-propanedinitrile (3) with 2, 3-dihydrofuran, has been catalytically hydrogenated to the α-(aminomethylene)-9-(tetrahydrofuran-2-yl)-9H-purine-6-acetonitrile (5) in good yield using N, N-dimethylformamide-benzene as a solvent over Pd-C under medium pressure. Substitution of 5 with amines gave the corresponding alkylaminomethylene purines (6 and 7). Reaction of 5 with hydrazine gave the pyrazole derivative (8).

著者

藤井 達也 西田 裕 阿比留 佳明 山本 雅司 黄瀬 正博

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.11, pp.1872-1877, 1995-11-15 (Released:2008-03-31)

参考文献数

13

被引用文献数

7 19

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Diisopropylamine (DIPA), N, N-diisopropylethylamine (DIPEA), tributylamine (TNBA) and 7-(1-piperazinyl)-4-quinolone-3-carboxylic acid (2) were titrated in water-dimethylformamide (DMF) mixtures containing 45-98% DMF. Apparent pKa values in anhydrous DMF (pKDMF) were calculated by extrapolation from the variation in the half-neutralization pH values in aqueous DMF. The validity of the relative basicity derived from the pKDMFs was confirmed by examination of the kinetics of esterification of a derivative of 2 with 4-(bromomethyl)-5-methyl-1, 3-dioxol-2-one (DMDO-Br). Relative basicities in DMF were : the carboxylate anion of 2»DIPA>DIPEA>TNBA >the amino group in the piperazinyl part of 2. This order is clearly different from that observed in water.We concluded that DIPEA is a suitable agent to suppress the undesired esterification during the reaction to mask the amino group of 2 with a DMDO group, because it does not remove a proton from the carboxyl group, but only from the protonated amino group.