薬剤学
Online ISSN : 2188-3149
Print ISSN : 0372-7629
ISSN-L : 0372-7629
63 巻 , 2 号
選択された号の論文の13件中1~13を表示しています
巻頭言
フォーラム
リレープラザ
R&D
 
一般論文
  • Katsutoshi Nakamura, Keiichi Tokihiro, Yukihisa Motomura, Satoshi Nish ...
    2003 年 63 巻 2 号 p. 65-70
    発行日: 2003年
    公開日: 2019/05/12
    ジャーナル フリー

    Minodronic acid, a new bisphosphonate, is susceptible to low levels of aluminum ions leaching from regular glass ampoules when in solution. This could lead to an increase in microscopic particles depending on the containers, formulations or storage conditions used. In this study, the compatibilities of three chemically-treated glass ampoules for minodronic acid solution were examined. The formulation that demonstrated a sudden particulate increase in regular glass ampoules after storage for 5 mo at 25°C was used as a test solution. The particulate generation in each ampoule was evaluated by a newly introduced stress test (4 freeze-thaw cycles after storage for 4 wk at 80°C) and a regular long-term test (storage for 6 mo at 25°C). The long-term test revealed that sulfur-treated ampoules and nitric acid-treated ampoules did not show the particulate increase even though silicone-treated ampoules did. In contrast, the stress test, which was designed to quickly choose robust formulations in regular glass ampoules, was inappropriate for choosing suitable ampoules because the results of the stress test did not correlate well with those of the long-term test due to the intense stress placed on the ampoules. SiO2-treated ampoules, which suppressed the particulate increase at 25°C, also generated an excess amount of particles after the stress test. It appears that the protective SiO2 layer was severely damaged due to the harsh temperature conditions.

  • Masaki Tokunaga, Masao Nagao, Mariko Nagata, Norio Hazemoto, Toshihisa ...
    2003 年 63 巻 2 号 p. 71-78
    発行日: 2003年
    公開日: 2019/05/12
    ジャーナル フリー

    This study examined the transfection activity and cytotoxicity of the synthetic polycationic peptides, poly (L-lysine), poly (L-ornithine), poly (L-arginine), poly (L-lysine, L-alanine), and poly (L-ornithine, L-leucine), on focusing the effect of molecular weight and concentration of the polypeptide on DNA transfection. The transfection activity was examined in terms of the functional transfer of pSV2cat plasmid DNA into HeLaS3 cells. Cell viability was evaluated by measuring the activity of the lactate dehydrogenase (LDH) released from cells. Poly (L-ornithine), poly (L-arginine) and poly (L-ornithine, L-leucine) induced very high expression levels of a foreign gene in HeLaS3 cells. However, poly (L-lysine) and poly (L-lysine, L-alanine) were not effective. Cytotoxicity was observed at high concentrations of polypeptides and increased in the order of poly (L-ornithine) > poly (L-lysine) > poly (L-arginine) ≥ poly (L-ornithine, L-leucine) > poly (L-lysine, L-alanine). The molecular weight of polypeptide also greatly influenced transfection activity. The higher molecular weight of poly (L-ornithine) (MW 203,400) mediated gene transfer most effectively, and its transfection activity were approximately 5-fold higher than that of poly (L-ornithine), with a molecular weight of 53, 600, whereas the poly (L-ornithine) of a lower molecular weight (MW 11,700) exhibited little activity. The optimal concentrations of the polypeptides depended on the DNA level in an applied solution. The optimal mass ratio of DNA/polypeptide for transfection was 0.4-0.8. The transfection activity of a polypeptide depends on its amino acid composition, molecular weight, and DNA/peptide ratio. High molecular poly (L-ornithine) and poly (L-arginine) were more efficient mediators of DNA transfection than Lipofectin, a commercially available reagent.

  • Yasuyuki Asai
    2003 年 63 巻 2 号 p. 79-88
    発行日: 2003年
    公開日: 2019/05/12
    ジャーナル フリー

    In order to develop an intravenous formulation of all-trans retinal (vitamin A aldehyde, VAA) for the treatment of night blindness, VAA and dipalmitoylphosphatidylcholine (DPPC) were sonicated and dispersions in the VAA mole fraction range of 0.1-0.7 were stable at room temperature for 3 days. In order to clarify the dispersal mechanism, the interaction between VAA and DPPC was investigated using several physicochemical techniques. Dynamic light scattering measurements showed that the diameter of the dispersed particles was 50-70 nm. A limited amount of VAA was incorporated into DPPC bilayer membranes (approximately 5 mole%). The trapped aqueous space marker calcein and the volume in the VAA/DPPC particles was decreased remarkably into small unilamellar vesicles of DPPC with the addition of VAA. The decline in the fraction of vesicular particles was also confirmed by fluorescence quenching of N-dansylhexadecylamine in the DPPC membrane by the addition of the quencher CuSO4. These results indicate that the excess VAA separated from the DPPC bilayers was stabilized as suspension particles by the DPPC surface monolayer. The monolayerbilayer equilibrium of VAA/DPPC mixtures was explored by measurements of spreading and collapse pressures.

ノート
feedback
Top