Nobuo Umeki
Taisho Pharmaceutical Co.
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International Journal of Pharmaceutics | 2010
Nobuo Umeki; Takayuki Sato; Masahiro Harada; Junko Takeda; Shuji Saito; Yasunori Iwao; Shigeru Itai
In order to achieve the sustained release of 3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio) thiophene-2-carboxamide (BFB0261), a new potent osteogenic compound for the treatment of bone disorders, we prepared microspheres containing BFB0261 and newly synthesized three poly (D, L-lactic acid) (PLA), four poly (D, L-lactic acid-co-glycolic acid) (PLGA), and eight poly (D, L-lactic acid)-block-poly(ethylene glycol) (PLA-PEG) biodegradable polymers or copolymers, and evaluated the release pattern of BFB0261 from the microspheres in vitro and in vivo. The mean particle size of the microspheres, except for the microspheres constructed from PLA-PEG with a greater than 20% PEG component, was in the range of approximately 10-50 microm, and the preparations showed a spherical shape with a smooth surface. In an in vitro release study, the release of BFB0261 from PLA-1 (Mw: 36 kDa), PLAPEG9604H (PLA/PEG ratio: 96:4, Mw: 181 kDa), or PLAPEG8317 (PLA/PEG ratio: 83:17, Mw: 106 kDa) microspheres occurred in a zero-order manner with a slow release, and more than 50% of BFB0261 remained in each type of microsphere at 12 weeks after incubation. When the BFB0261 microspheres constructed from various polymers were intramuscularly administered to the rat femur, the microspheres constructed from PLA-1 or PLAPEG9604H were able to achieve a sustained release of BFB0261 at the injection site for 6 weeks. The present information indicates that microspheres constructed from PLA-1 or PLAPEG9604H may be feasible for bone engineering.
International Journal of Pharmaceutics | 2011
Nobuo Umeki; Takayuki Sato; Masahiro Harada; Junko Takeda; Shuji Saito; Yasunori Iwao; Shigeru Itai
To achieve sustained release of 3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio) thiophene-2-carboxamide (BFB0261), a new potent osteogenic compound for treating bone disorders, we prepared film formulations containing BFB0261 and the following newly synthesized biodegradable polymers by a solvent casting technique: poly(D,L-lactic acid) (PLA), poly(D,L-lactic acid-co-glycolic acid) (PLGA), poly(D,L-lactic acid)-block-poly(ethylene glycol) (PLA-PEG), and poly(D,L-lactic acid-co-trimethylene carbonate) (PLA-TMC) polymers or copolymers. Powder X-ray diffractometry (PXRD), differential thermal analysis (DTA), scanning electron microscopy (SEM), and tensile testing were performed to examine the physicochemical properties of these films. Almost all the films exhibited a smooth and homogeneous surface, as observed by SEM. In addition, PXRD and DTA revealed that BFB0261 existed in an amorphous state in the films. The in vitro release of BFB0261 from PLA100 (M(w): 251 kDa), PLAPEG9604H (PLA/PEG ratio: 96:4; M(w): 181 kDa), PLAPEG8515H (PLA/PEG ratio: 85:15; M(w): 51.5 kDa), or PLAPEG8020 (PLA/PEG ratio: 80:20; M(w): 33.7 kDa) films followed zero-order kinetics with slow release up to 12 weeks following incubation. Although release of BFB0261 from PLA-TMC films followed first-order kinetics, sustained release of BFB0261 for 12 weeks was still observed for PLATMC8416 (PLA/TMC ratio: 84:16; M(w): 170 kDa) films. Furthermore, when the BFB0261-loaded films constructed from various polymers were implanted subcutaneously on rat backs, the PLAPEG8515H and PLATMC8416 films were capable of achieving sustained release of BFB0261 at the administrated site for 12 weeks. Therefore, the present data indicate that films constructed from PLAPEG8515H or PLATMC8416 may be applicable to bone or tissue engineering.
Archive | 1993
Toshio Yajima; Kuniaki Ishii; Nobuo Umeki; Shigeru Itai; Hidefumi Hayashi; Kimihide Shimano; Ikuo Koyama
Chemical & Pharmaceutical Bulletin | 1999
Toshio Yajima; Nobuo Umeki; Shigeru Itai
Chemical & Pharmaceutical Bulletin | 1996
Toshio Yajima; Akemi Nogata; Miki Demachi; Nobuo Umeki; Shigeru Itai; Nobuo Yunoki; Masami Nemoto
Archive | 1993
Toshio Yajima; Kuniaki Taisho Pharmaceu Ishii; Nobuo Umeki; Shigeru Itai; Hidefumi Hayashi; Kimihide Shimano; Ikuo Koyama
Drug Metabolism and Pharmacokinetics | 2002
Nobuo Umeki; Yoshiki Fukasawa; Sumio Ohtsuki; Satoko Hori; Yuki Watanabe; Yoshiro Kohno; Tetsuya Terasaki
Journal of The Society of Powder Technology, Japan | 1988
Tooru Maki; Nobuo Umeki; Yasuo Ozawa
Archive | 1993
Hidefumi Hayashi; Kuniaki Ishii; Shigeru Itai; Ikuo Koyama; Kimihide Shimano; Nobuo Umeki; Toshihisa Yajima; 郁夫 小山; 公秀 島野; 茂 板井; 英文 林; 伸夫 梅木; 稔央 矢島; 邦明 石井
Archive | 1992
Shusei Ito; Shigeru Itai; Nobuo Umeki