• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.404.1-404.1
• /
• 2002

A LC/MS/MS method for the simultaneous determination of the activities of seven major human drug-metabolizing cytochrome P450s (CYP3A4. CYP2D6. CYP2C9. CYP1A2, CYP2C19, CYP2A6. and CYP2C8) was developed. This method used an in vitro cocktail of specific substrates (midazolam. bufuralol. diclofenac, ethoxyresorufin. S-mephenYlOin. coumarin. and paclitaxel) and LC/MS/MS. The assay incubation time is 20 min and the analysis time is 8 min/sample. (omitted)

• 한국결정학회:학술대회논문집
• /
• 한국결정학회 2002년도 정기총회 및 추계학술연구발표회
• /
• pp.19-19
• /
• 2002

Perovskite-type titanate dielectrics have attracted much attention in memory devices such as DRAMs or FeRAMs due to their high dielectric constants. However, low volatility of the Ba, Sr, Pb or Zr precursors with only thd ligands has limitations in obtaining high quality thin films by liquid source metal organic chemical vapor deposition (LS-MOCVD) processes. To improve the volatility of these precursors, many attempts have been made such as adding polyether ligands to satisfy the coordinative saturation. We report the synthesis of new precursors Ba(thd)₂(tmeea) and Sr(thd)₂(tmeea), where tmeea = tris[2-(2-methoxyethoxy)ethyl]amino, and LS-MOCVD of barium strontium titanate (BSTO) thin films using these precursors. Due to increased basicity of amines compared with ethers, it is expected that the nitrogen-donor ligand will make a strong bond to a metal than an analogous oxygen-donor ligand, consequently improving the volatility and thermal behavior of these precursors. Thin films of BSTO were grown on Pt(111)/SiO₂/Si(100) substrates by LS-MOCVD using a cocktail source consisting of the conventional Ti precursor Ti(thd)₂(O/sup i/Pr), and these new Ba and Sr precursors. As-grown films were characterized by XPS, SEM, XRD, XRF, and C-V and I-V measurements. BSTO films grown at 420℃ were stoichiometric barium strontium titanate with very smooth surface morphology and their dielectric constants were found to be as targe as 450. Dependence of the composition, microstructure and the electrical properties of the BSTO films on the growth temperature, annealing temperature, working pressure, and the composition of the cocktail source will be discussed.

• Mass Spectrometry Letters
• /
• 제8권4호
• /
• pp.98-104
• /
• 2017

Ginseng (Panax ginseng Meyer) is a well-known health functional food used as a traditional herbal drug in Asian countries owing to its diverse pharmacological effects. Herb-drug interactions may cause unexpected side effects of co-administered drugs by the alteration of pharmacokinetics through effects on cytochrome P450 activity. In this study, we investigated the herb-drug interactions between Korean red ginseng extract (KRG) and five CYP-specific probes in mice. The pharmacokinetics of KRG extract induced-drug interactions were studied by cassette dosing of five CYP substrates for CYP1A, 2B, 2C, 2D, and 3A and the LC-MS/MS analysis of the blood concentration of metabolites of each of the five probes. The linearity, precision, and accuracy of the quantification method of the five metabolites were successfully confirmed. The plasma concentrations of five metabolites after co-administration of different doses of the KRG extract (0, 0.5, 1, and 2 g/kg) were quantified by LC-MS/MS and dose-dependent pharmacokinetic parameters were determined. The pharmacokinetic parameters of the five metabolites were not significantly altered by the dose of the KRG extract. In conclusion, the single co-administration of KRG extract up to 2 g/kg in vivo did not cause any significant herb-drug interactions linked to the modulation of CYP activity.

• 한국미생물·생명공학회지
• /
• 제41권2호
• /
• pp.236-241
• /
• 2013

필로카르핀은 Pilocarpus 속으로부터 유일하게 분리되는 이미다졸계 알칼로이드로서 상당히 제약적으로 중요하다. Pilocarpus jaborandi로부터 필로카르핀을 추출하기 위하여 환경친화적인 효소를 이용한 추출법을 이용하였다. 본 연구에서는 상업적으로 이용할 수 있는 효소칵테일인 Viscozyme$^{(R)}$L을 사용하였다. 추출 조건은 기질, 효소, 온도 및 pH 등에 기초하여 최적화되었다. 가장 높은 수율을 위한 최적화 조건은 pH4인 50 mM 아세트산 40 ml 하에서 $45^{\circ}C$, 100 mg 기질, 30시간 반응이였다. 최적의 추출 효소농도는 10%이였다. Viscozyme$^{(R)}$L 처리로부터 얻어진 전체 필로카르핀 함유량($1.14{\mu}g/mg$) 수준은 기존 처리방법에서 얻어지는 양($0.37{\mu}g/mg$)보다 3.08배 높은 것을 확인하였다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제29권11호
• /
• pp.1576-1584
• /
• 2016

Acetyl xylan esterase (AXE), which hydrolyzes the ester linkages of the naturally acetylated xylan and thus known to have an important role for hemicellulose degradation, was isolated from the anaerobic rumen fungus Neocallimastix frontatlis PMA02, heterologously expressed in Escherichi coli (E.coli) and characterized. The full-length cDNA encoding NfAXE1 was 1,494 bp, of which 978 bp constituted an open reading frame. The estimated molecular weight of NfAXE1 was 36.5 kDa with 326 amino acid residues, and the calculated isoelectric point was 4.54. The secondary protein structure was predicted to consist of nine ${\alpha}$-helixes and 12 ${\beta}$-strands. The enzyme expressed in E.coli had the highest activity at $40^{\circ}C$ and pH 8. The purified recombinant NfAXE1 had a specific activity of 100.1 U/mg when p-nitrophenyl acetate (p-NA) was used as a substrate at $40^{\circ}C$, optimum temperature. The amount of liberated acetic acids were the highest and the lowest when p-NA and acetylated birchwood xylan were used as substrates, respectively. The amount of xylose released from acetylated birchwod xylan was increased by 1.4 fold when NfAXE1 was mixed with xylanase in a reaction cocktail, implying a synergistic effect of NfAXE1 with xylanase on hemicellulose degradation.

• Journal of Ginseng Research
• /
• 제40권4호
• /
• pp.375-381
• /
• 2016

Background: We evaluated the drug interaction profile of Red Ginseng (RG) with respect to the activities of major cytochrome P450 (CYP) enzymes and the drug transporter P-glycoprotein (P-gp) in healthy Korean volunteers. Methods: This article describes an open-label, crossover study. CYP probe cocktail drugs, caffeine, losartan, dextromethorphan, omeprazole, midazolam, and fexofenadine were administered before and after RG supplementation for 2 wk. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data using analysis of variance after RG administration versus before RG administration. Results: Fourteen healthy male participants were evaluated, none of whom were genetically defined as poor CYP2C9, 2C19, and CYP2D6 metabolizers based on genotyping. Before and after RG administration, the geometric least-square mean metabolic ratio (90% CI) was 0.870 (0.805-0.940) for caffeine to paraxanthine (CYP1A2), 0.871 (0.800-0.947) for losartan (CYP2C9) to EXP3174, 1.027 (0.938-1.123) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.373 (0.864-2.180) for dextromethorphan to dextrorphan (CYP2D6), and 0.824 (0.658-1.032) for midazolam (CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time ($AUC_{last}$) for fexofenadine (P-gp) was 0.963 (0.845-1.098). Administration of concentrated RG for 2 wk weakly inhibited CYP2C9 and CYP3A4 and weakly induced CYP2D6. However, no clinically significant drug interactions were observed between RG and CYP and P-gp probe substrates. Conclusion: RG has no relevant potential to cause CYP enzyme- or P-gp-related interactions.

• Mass Spectrometry Letters
• /
• 제5권3호
• /
• pp.84-88
• /
• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.