|関連生薬||鳥頭 , 附子 , 炮附子|
|参考文献||1) Kawata Y., Ma C. M., Meselhy M. R., Nakamura N., Wang H., Hattori M., Namba T., Satoh K., and Kuraishi Y.: Conversion of aconitine to lipoaconitine by human intestinal bacteria and their anti-nociceptive effects in mice. J. Trad. Med., 16, 15-23 (1999).
2) Tazawa T., Zhao H., Li Y., Meselhy M. R., Nakamura N., Akao T. and Hattori M.: A new enzyme immunoassay for aconitine and its application to quantitative determination of aconitine levels in plasma. Biol. Pharm. Bull., 26, 1289-1294 (2003).
3) Zuo F., Zhao J., Nakamura N., Gao J. J., Akao T., Hattori M., Oomiga Y., and Kikuchi Y.: Pharmakokinetic stydy of benzoylmesaconine in rats using an enzyme immunoassay system. J. Nat. Med., 60, 313-321 (2006).
4) Fan Zhanga, Ming-hai Tanga, Li-juan Chena, Rui Li, Xian-huoWang, Jun-guo Duan, Xia Zhao, Yu-quanWei, Simultaneous quantitation of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography–tandem mass spectrometry and pharmacokinetics evaluation of “SHEN-FU” injectable powder. J. Chromato. B, 873, 173–179 (2008).
5) Fan Zhang, Ming-hai Tang, Li-juan Chen, Rui Li, Xian-huoWang, Jun-guo Duan, Xia Zhao, Yu-quan Wei, Simultaneous quantitation of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography–tandem mass spectrometry and pharmacokinetics evaluation of “SHEN-FU” injectable powder. J. Chromato. B, 873, 173–179 (2008).
6) Ling Ye, Tao Wang, Caihua Yang, Lan Tang, Juan Zhou, Chang Lv, Yun Gong, Zhihong Jiang, Zhongqiu Liu, Microsomal cytochrome P450-mediated metabolism of hypaconitine, an active and highly toxic constituent derived from Aconitum species. Toxicology Letters 204, 81–91 (2011).
7) Yang Yang, Juan Chen, Yan-Ping Shi, Determination of aconitine, hypaconitine and mesaconitine in urine using hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography. Journal of Chromatography B, 878, 2811–2816 (2010).
8) Bo Sun, Shengming Wu, Ling Li, Haijing Li, Qi Zhang, Hebing Chen, Famei Li, Fangting Dong and Xianzhong Yan, A metabolomic analysis of the toxicity of Aconitum sp. alkaloids in rats using gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 23, 1221–1228 (2009).
|論文備考||※Quantitative determination of aconitine (1) in plasma after intravenous administration to rats
Aconitine (1, 0.1 mg) was dissolved in DMSO (250 ml) and diluted with saline to a total volume of 5 ml. A portion of the solution was injected through tail vein to rats at a dose of 0.02 mg aconitine/kg b.w. The blood samples were repeatedly collected through tail vein at 5, 15 and 30 min, and then 1, 2, 4, 6 and 8 hr after intravenous administration. The samples were centrifuged at 1,100 × g, 15 min and 4C to give the respective plasma. The original plasma or 10-fold diluted ones (5 ml) were used for EIA to determine aconitine levels. The standard calibration curve ranging from 0.1 ~ 1000 pg aconitine/tube was prepared in the presence of the plasma from conventional rats. [Tazawa et al., Biol. Pharm. Bull., 26, 1289-1294 (2003)]
※Procedure of enzyme immunoassay (EIA)
Samples or standard solutions containing various amounts of aconitine (1) were incubated with an antiserum (50 ml) and a 103-fold diluted b-Gal conjugate (25 ml) at room temperature for 2 h. Then, 10-fold diluted goat anti-rabbit Ig G (20 ml) and 100-fold diluted normal rabbit serum (20 ml) were added to the reaction mixture. The mixture was kept overnight at 4°C. After addition of buffer A (1 ml), the resulting mixture was centrifuged at 1,100 × g for 15 min at 4°C. The supernatant was discarded, and the precipitates were washed with buffer A followed by incubation with 01 mM 4-methylumbelliferyl β-D-galactoside for 30 min at 30°C. The reaction was stopped by the addition of 100 mM glycine-NaOH buffer, pH 10.3, (4 ml). The fluorescence intensity of a product (4-methylumbelliferone) was spectrofluorometrically measured at wavelengths of 365 nm (excitation) and 448 nm (emission). [Tazawa et al., Biol. Pharm. Bull., 26, 1289-1294 (2003)]
※Quantitative determination of aconitine (1) level in plasma after oral administration to rats
Aconitine (1, 0.01 mg/ml) dissolved in DMSO-H2O (1:19) was orally administered to four rats at a dose of 0.1 mg/kg b.w. The blood samples were repeatedly collected through tail vein at 5, 15 and 30 min, and then 1, 2, 4, 6 and 8 hr after oral administration, and centrifuged at 1,100 × g, for 15 min at 4°C to give the respective plasma. The original plasma (5 ml) was subjected to EIA for quantitative determination of aconitine. [Tazawa et al., Biol. Pharm. Bull., 26, 1289-1294 (2003)]
※Quantitatively determined by the respective enzyme immunoassay systems. [Zuo et al., J. Nat. Med., 60, 313-321 (2006)]
※“SHEN-FU” injectable powder were applied to 18 healthy volunteersby intravenous drop infusion. Six volunteers were involved in each experiment. The blood samples were collected at intervals after intravenous drop infusion. The pharmacokinetics demonstrated that the concentrations of aconitine, mesaconitine, and hypaconitine were at very low levels with < 0.2, < 0.2, and < 0.7 ng/mL or under detection limit for all) and the content of benzoylmesaconine was highest. [Fan Zhang et al., J. Chromato. B, 873, 173–179 (2008).]