Hiratsuka, Japan
Hiratsuka, Japan

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Suzuki Y.,DaiichiSankyo Co. | Kato T.,DaiichiSankyo Co. | Kikkawa Y.,DaiichiSankyo Co. | Suzuki T.,DaiichiSankyo Co. | And 2 more authors.
Powder Technology | Year: 2015

In the pharmaceutical lubricant mixing process, lubricity of granules after mixing was evaluated by measuring the contact angle with water and tablet hardness. The granules were prepared using three different types of popular tumble mixers; V-blender (effective volumetric capacity: 70. L), Container blender (36. L) and Bin blender (20. L) with different powder loading rates (10-88%), blender rotation speeds (18-37. rpm) and mixing times (5-120. min) for model placebo formulation. Contact angle measurement and tablet hardness are useful as alternative characteristics for evaluation of granule lubricity. Based on the experimental data, mixing performance index (MPI), which is an empirical equation including blender type, powder loading ratio, mixing rotation speed and batch size as functional parameters, was developed. Mixing ability (MA) was defined by the combination of MPI and mixing time. Calculated MA exhibited good correlation with tablet hardness (correlation coefficient is 0.89) in all datasets. MA was verified by nine different drug product data with different manufacturing scales, to enable the MA model to support the formulation researcher to set mixing process parameters when the batch size or blender type changes. © 2015.


Morishima Y.,DaiichiSankyo Co. | Kamisato C.,DaiichiSankyo Co. | Honda Y.,DaiichiSankyo Co.
European Journal of Pharmacology | Year: 2014

Edoxaban is an oral and direct activated factor X inhibitor. In this study, the acute treatment effect of edoxaban on venous thrombosis is investigated in rats by single and multiple administrations, and compared to the conventional parenteral anticoagulants, enoxaparin and fondaparinux. Venous thrombus was induced in the inferior vena cava by partial stenosis plus topical application of 10% ferric chloride for 5 min. After 1-h thrombus maturation, oral edoxaban and subcutaneous enoxaparin and fondaparinux were given. In the single administration experiment, thrombus weight was measured 1 or 4 h after thrombus induction. In the multiple administration experiments, edoxaban was orally administered once daily (QD) and twice daily (BID) for 3 days. In the single administration experiment, oral administration of edoxaban (3.0 and 10 mg/kg) 1 h after thrombus formation significantly regressed the venous thrombus compared to the thrombus at 1 h after thrombus formation. Similarly the significant venous thrombus regression was observed with enoxaparin (10 mg/kg) and fondaparinux (0.30-3.0 mg/kg). In the multiple administration experiment, both QD and BID administration of edoxaban at daily doses of 5 and 10 mg/kg exerted significant treatment effects. QD administration of edoxaban including lower doses (1-10 mg/kg) significantly reduced thrombus weight. Edoxaban administered QD and BID was effective in the treatment of venous thrombosis, and the treatment effect of edoxaban was comparable to the conventional parenteral anticoagulants. These data demonstrate the potential of edoxaban as an oral anticoagulant in the acute treatment of venous thromboembolism. © 2014 Elsevier B.V. All rights reserved.


Nishimiya D.,Biologics | Mano T.,Chiyoda Corporation | Miyadai K.,Chiyoda Corporation | Yoshida H.,DAIICHISANKYO CO. | Takahashi T.,Biologics
Applied Microbiology and Biotechnology | Year: 2013

Secretory capacities including folding and assembly are believed to be limiting factors in the establishment of mammalian cell lines producing high levels of recombinant therapeutic proteins. To achieve industrial success, it is also important to improve protein folding, assembly, and secretory processes in combination with increasing transcription and translation. Here, we identified the expression of CHOP/Gadd153 and GRP78, which are unfolded protein response (UPR)-related genes, correlated with recombinant antibody production in stable CHO cells. Subsequently, CHOP overexpression resulted in increasing recombinant antibody production in some mammalian cell lines, and in addition a threefold further enhancement was obtained by combining expression with UPR-related genes or ER chaperones in transient assays. Overexpression of CHOP had no effect on the biochemical characteristics of the product. These results suggest overexpression of CHOP and its combinations may be an effective method to efficiently select a single cell line with a high level of antibody production in the development of cell lines for manufacturing. © 2012 Springer-Verlag.


Kobayashi N.,DaiichiSankyo Co.
Bioanalysis | Year: 2014

At the 5th Japan Bioanalysis Forum symposium, distinguished bioanalytical scientists from government and industry commentated on the bioanalytical method validation guidelines/guidance issued by their own regions, including the draft bioanalytical method validation guideline for ligand binding assay by the Japanese Ministry of Health, Labour and Welfare, which was finalized in April 2014. Additionally, the Japan Bioanalysis Forum Discussion Group, in which daily bioanalytical issues/interests were scientifically discussed, picked up five topics, and more than 200 conference attendees openly exchanged their views on a wide range of bioanalytical issues with discussion group members. This manuscript provides an overview of the highlights out of the symposium. © 2014 Future Science Ltd.


Namba E.,DaiichiSankyo Co. | Okumura R.,DaiichiSankyo Co. | Chiba M.,Daiichi Sankyo | Hoshino K.,Daiichi Sankyo | Tateda K.,Toho University
Japanese Journal of Antibiotics | Year: 2013

We evaluated the in vitro activity of sitafloxacin against Japanese clinical isolates of Streptococcus pyogenes by broth microdilution susceptibility testing and time-kill studies to elucidate its eradication potential against S. pyogenes. One hundred and nineteen clinical isolates of S. pyogenes isolated from pharynx were tested to sitafloxacin and seven other agents in the susceptibility testing. The time-kill studies were conducted with five strains, one of which was resistant to clarithromycin, one resistant to levofloxacin and one type strain of S. pyogenes. In the time-kill studies, sitafloxacin, garenoxacin, amoxicillin and clarithromycin were assessed at static concentrations of their respective peak concentrations in plasma (C max) when administered as oral single doses for adult patients with S. pyogenes infections. We found the rank order of antimicrobial activity against S. pyogenes isolates was: cefcapene (MIC90, 0.015 μg/mL) > amoxicillin (0.03 μg/mL) > sitafloxacin (0.12 μg/mL) > garenoxacin (0.25 μg/mL) > levofloxacin (4 μg/mL) > minocycline (16 μg/mL). Macrolide-resistant isolates accounted for 72 (60.5%), resulting in clarithromycin and azithromycin MIC90s of >32 and >128//g/mL, respectively. Sitafloxacin exhibited the most rapid bactericidal activity (≥3 log reduction from the initial inoculum) within 2 h against all tested strains, including even one levofloxacin-resistant strain. For garenoxacin, bactericidal activity was achieved between 2 and 6 h. Amoxicillin revealed no significant bactericidal activity up to 6 h. Clarithromycin showed no bactericidal activity and did not inhibit growth of a clarithromycin-resistant strain. These data indicate the potential usefulness of sitafloxacin for the treatment of S. pyogenes eradication.


PubMed | DaiichiSankyo Co.
Type: Journal Article | Journal: Cell biology international | Year: 2010

We have demonstrated that a unique megakaryocytic cell line UT-7/TPO could respond to one of the primary platelet signals through GP (glycoprotein) VI and a secondary signal of the AA (arachidonic acid) cascade. Unlike other megakaryocytic cell lines, UT-7/TPO was found to express GPVI and its associate signal molecule of FcRgamma (Fc receptor gamma chain). When UT-7/TPO was stimulated with the GPVI agonist convulxin, the [Ca2+]i (intracellular Ca2+) was elevated in a convulxin concentration-dependent manner, and [Ca2+]i elevation was blocked by pretreatment with the Src family kinase inhibitor PP2 and the phospholipase inhibitor U73122. These results strongly indicate that endogenously expressed GPVI signal molecules are functional in UT-7/TPO. Concerning the AA cascade, the expression of COX (cyclooxygenase)-1 and TX (thromboxane) synthase was observed, and this cell line was able to produce TX by exogenous AA, followed by [Ca2+]i elevation mediated through the TX receptor. It is worth noting that convulxin stimulation did not cause TX generation, even through the GPVI pathway and the AA cascade are functional in this cell line. As there are many reports that convulxin-stimulated platelets failed to produce TX, it is suggested that UT-7/TPO has the same property as the platelets in regards to convulxin stimulation. Thus, UT-7/TPO is useful for the observation of both the GPVI pathway and AA cascade without requiring either the induction of differentiation or GPVI transfection. Furthermore, this cell line provides a new tool for research on platelet activation signals.

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