• 제목/요약/키워드: $E_{MAX,1kV}$

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Rapid and Simple Method for the Determination of Pregabalin in Human Plasma using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS): Application to a Bioequivalence Study of Daewoong Pregabalin Capsule To Lyrica® Capsule (Pregabalin 150 mg)

  • Jang, Ki-Ho;Seo, Ji-Hyung;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • 제41권4호
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    • pp.255-262
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    • 2011
  • Method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of pregabalin in plasma samples. Acquisition was performed by monitoring the transitions: m/z 160.1${\rightarrow}$142.2 for pregabalin and m/z 423.2${\rightarrow}$207.1 for losartan (as an internal standard). After cold acetonitrileinduced protein precipitation of the plasma samples, separation was performed with C18 column by isocratic mobile phase consisted of 10 mM ammonium acetate and acetonitrile (15:85, v/v). Results were linear over the concentration ranged from 0.1 to $10{\mu}g$/mL and the correlation coefficients (r) were $\geq0.99$. Intra- and inter-day precisions were $\leq6.02$ and $\leq11.04%$, respectively, and intra- and inter-day accuracies were 96.60-101.09 and 98.10-102.60%, respectively. This validated method was successfully applied to a bioequivalence study of two formulations of pregabalin, Daewoong pregabalin capsule (Daewoong Pharm. Co., Ltd.) and Lyrica$^{(R)}$ capsule (Pfizer Korea Ltd.) in twenty eight healthy Korean volunteers. The subjects received a single oral dose of each formulation (150 mg as pregabalin) in a randomized $2{\times}2$ crossover study and plasma samples were obtained from each subject at predetermined time intervals. Then, the pharmacokinetic parameters ($AUC_{0-t}$, $C_{max}$ and $T_{max}$) were calculated and statistically analyzed to assess the differences between two formulations. The 90% confidence intervals for the log-transformed data were acceptable range of log 0.8-log 1.25 (e.g., log 1.0048-log 1.0692 for AUC0-t, log 0.9142-log 1.0421 for $C_{max}$). Thus, $AUC_{0-t}$ and $C_{max}$ met the criteria of the Korea Food and Drug Administration (KFDA) for bioequivalence test indicating that Daewoong pregabalin capsule was bioequivalent to Lyrica$^{(R)}$ capsule.

재조합균주 E. coli CNU312가 생산하는 Catechol 2,3-Dioxygenase의 정제 및 특성 (Purification and Characterization of Catechol 2,3-Dioxygenase from Recombinant Strain E. coli CNU312.)

  • 임재윤;최경호;최병돈
    • 미생물학회지
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    • 제36권1호
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    • pp.26-32
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    • 2000
  • Toluene, phenyl 등의 분해균주인 Burkholderia cepacia G4로부터 tomB 유전자를 클로닝하여 얻은 재조합 균주 E. coli CNU312로부터 catechol 2,3-dioxygenase를 정제하여 효소학적 특성을 조사하였다. Catechol 2,3-dioxygenase는 native 분자량이 약 140.4 kDa이었으며 4개의 동일한 35 kDa subunit로 구성된 homotetramer로 생각된다. Catechol의 $K_(m)$값과 $V_(max)$값은 372.6 $\mu$M과 39.27 U/mg이었으며, 1.56 mM 이상의 기질 농도에서는 활성이 감소되었다. 효소 활성의 최적 pH는 8.0이었으며, pH 7.0-8.0 범위에서 안정하였다. 최적 활성온도는 $40^{\circ}C$였으며, $60^{\circ}C$이상에서 완전히 활성을 상실하였다. 또한 $Fe^(2+)$, $Fe^(3+)$ 를 비롯한 대부분의 금속 이온에 의해 활성이 감소되었으며, $Mg^(2+)$, $K^(+)$에는 영향을 받지 않았다. 효소 활성부위를 알아보기 위해 화학변형제를 처리한 결과, tryptophan과 histidine이 효소 활성부위에 존재하는 것으로 추정된다. 그리고 10%의 유기용매에 안정성을 보이지 않았으며, $H_(2)$$O_(2)$, EDTA, ο-phenanthroline에도 활성이 감소되었다. 또한 2-mercaptoethanol, dithiothreitol, 그리고 ascorbic acid와 같은 환원제에 대해서도 안정성을 보이지 않았다. 이 효소는 catechol에 대해 높은 기질 특이성을 보였으며, 3-methylcatechol, 4-methylcatechol, 그리고 4-chlorocatechol에 대해 약간의 활성을 보였다. 그러나 2,3-dihydroxybiphenyl에 대해서는 거의 활성을 보이지 않았다.

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$RuO_2$ Related Schottky contact for GaN/AlGaN device

  • Jung, Byung-Kwon;Kim, Jung-Kyu;Lee, Jung-Hee;Hahm, Sung-Ho
    • 한국반도체및디스플레이장비학회:학술대회논문집
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    • 한국반도체및디스플레이장비학회 2002년도 추계학술대회 발표 논문집
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    • pp.85-90
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    • 2002
  • $RuO_2$/GaN and related contacts were investigated for Schottky contacts in GaN-Based optical and electronic devices. We demonstrated that an $RuO_2$ film forms a stable Schottky contact on a GaN layer with a barrier height (${\Phi}_B$) of 1.46 eV and transmittance of 70% in the visible and near UV region. $RuO_2$/GaN Schottky diode showed a breakdown at over -50V and leakage current of only 0.3 nA at -5V. The $RuO_2$/GaN Schottky type photodetector had the UV/Visible rejection ratio of over $10^5$ and the responsivity of 0.23 A/W at 330 nm. The $RuO_2$ gate AlGaN/GaN EFET exhibited high drain current ($I_d$) of 689.3 mA/mm and high transconductance ($g_m$) of 197.4 mS/mm. Cut-Off frequency ($f_t$) and maximum operating frequency ($f_{max}$) were measured as 27.0 GHz and 45.5 GHz, respectively.

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Bioequivalence Study of Toriem® Tablet to Motilium-M® Tablet (Domperidone Maleate 12.72 mg) Evaluated by Liquid Chromatography/Tandem Mass Spectrometry

  • Ryu, Ju-Hee;Choi, Sang-Jun;Lee, Myung-Jae;Lee, Jin-Sung;Kang, Jong-Min;Tak, Sung-Kwon;Seo, Ji-Hyung;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • 제39권1호
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    • pp.65-71
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    • 2009
  • The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

무연 완화형/정규 강유전체 복합소재 [0.97Bi1/2(Na0.78K0.22)1/2TiO3-0.03LaFeO3]-Bi1/2(Na0.82K0.18)1/2TiO3의 저전계 전계유기 변형 특성 연구 (Tailoring Low-field Strain Properties of [0.97Bi1/2(Na0.78K0.22)1/2TiO3-0.03LaFeO3]-Bi1/2(Na0.82K0.18)1/2TiO3 Lead-Free Relaxor/Ferroelectric Composites)

  • 홍창효;강진규;조욱;이재신
    • 한국전기전자재료학회논문지
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    • 제29권6호
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    • pp.342-347
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    • 2016
  • We investigated the effect of $Bi_{1/2}(Na_{0.82}K_{0.18})_{1/2}TiO_3$ (BNKT) modification on the ferroelectric and electric-field-induced strain (EFIS) properties of lead-free $0.97Bi_{1/2}(Na_{0.82}K_{0.18})_{1/2}TiO_3-0.03LaFeO_3$ (BNKTLF) ceramics as a function of BNKT content (x= 0, 0.1, 0.2, 0.3, 0.5, and 1). BNKT-modified BNKTLF powders were synthesized using a conventional solid-state reaction method. As the BNKT content x increased from 0 to 1 the normalized electric-field-induced strain ($S_{max}/E_{max}$) was observed to increase at relatively low fields, i.e., below the poling field. Moreover, BNKTLF-30BNKT showed about 460 pm/V as low as at 3 kV/mm, which is a considerably high value among the lead-free systems reported so far. Consequently, it was confirmed that ceramic-ceramic composite, a mixture of an ergodic relaxor matrix and embedded ferroelectric seeds, is a salient way to make lead-free piezoelectrics practical with enhanced EFIS at low field as well as less hysterical.

SMALL DATA SCATTERING OF HARTREE TYPE FRACTIONAL SCHRÖDINGER EQUATIONS IN DIMENSION 2 AND 3

  • Cho, Yonggeun;Ozawa, Tohru
    • 대한수학회지
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    • 제55권2호
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    • pp.373-390
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    • 2018
  • In this paper we study the small-data scattering of the d dimensional fractional $Schr{\ddot{o}}dinger$ equations with d = 2, 3, $L{\acute{e}}vy$ index 1 < ${\alpha}$ < 2 and Hartree type nonlinearity $F(u)={\mu}({\mid}x{\mid}^{-{\gamma}}{\ast}{\mid}u{\mid}^2)u$ with max(${\alpha}$, ${\frac{2d}{2d-1}}$) < ${\gamma}{\leq}2$, ${\gamma}$ < d. This equation is scaling-critical in ${\dot{H}}^{s_c}$, $s_c={\frac{{\gamma}-{\alpha}}{2}}$. We show that the solution scatters in $H^{s,1}$ for any s > $s_c$, where $H^{s,1}$ is a space of Sobolev type taking in angular regularity with norm defined by ${\parallel}{\varphi}{\parallel}_{H^{s,1}}={\parallel}{\varphi}{\parallel}_{H^s}+{\parallel}{\nabla}_{{\mathbb{S}}{\varphi}}{\parallel}_{H^s}$. For this purpose we use the recently developed Strichartz estimate which is $L^2$-averaged on the unit sphere ${\mathbb{S}}^{d-1}$ and utilize $U^p-V^p$ space argument.

A New Salt-Tolerant Thermostable Cellulase from a Marine Bacillus sp. Strain

  • dos Santos, Yago Queiroz;de Veras, Bruno Oliveira;de Franca, Anderson Felipe Jacome;Gorlach-Lira, Krystyna;Velasques, Jannaina;Migliolo, Ludovico;dos Santos, Elizeu Antunes
    • Journal of Microbiology and Biotechnology
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    • 제28권7호
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    • pp.1078-1085
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    • 2018
  • A salt-tolerant cellulase secreted by a marine Bacillus sp. SR22 strain with wide resistance to temperature and pH was purified and characterized. Its approximate mass was 37 kDa. The endoglucanase, named as Bc22Cel, was purified by ammonium sulfate precipitation, gel filtration chromatography, and extraction from the gel after non-reducing sodium dodecyl sufate-polyacrylamide gel electrophoresis. The optimal pH value and temperature of Bc22Cel were 6.5 and $60^{\circ}C$, respectively. The purified Bc22Cel showed a considerable halophilic property, being able to maintain more than 70% of residual activity even when pre-incubated with 1.5 M NaCl for 1 h. Kinetic analysis of the purified enzyme showed the $K_m$ and $V_{max}$ to be 0.704 mg/ml and $29.85{\mu}mol{\cdot}ml^{-1}{\cdot}min^{-1}$, respectively. Taken together, the present data indicate Bc22Cel as a potential and useful candidate for industrial applications, such as the bioconversion of sugarcane bagasse to its derivatives.

녹조 납작파래 (Enteromorpha compressa)의 질산염 흡수, 배아 생장 및 지방산 조성에 대한 광 및 온도의 영향 (Effects of Light and Temperature on Nitrate Uptake, Germling Growth and Fatty Acid Composition of Enteromorpha compressa (Chlorophyta))

  • 이동훈;이순정;류진아;박은정;남기완
    • 한국수산과학회지
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    • 제37권1호
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    • pp.57-64
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    • 2004
  • Effects of light and temperature on the nitrate uptake and germling growth of Enteromorpha compressa (L.) Greville (Chlorophyta) were studied based on samples from Cheongsapo near Busan, Korea. In addition, their effects on fatty acids composition in thallus were examined. Nitrate uptake showed saturation kinetics. $V_{max}$ (maximal uptake rate) and its $K_s$ (half-saturation constant) at $20^{\circ}C,\;80\;{\mu}mol\;m^{-2}s^{-1},$ white light were $1.571\;{\mu}mol{\cdot}g\;fr\;wt^{-1}{\cdot}h^{-1}$ and 3.56 ${\mu}M$, respectively. In nitrate uptake with irradiance, wavelength and temperature, its rate represented respectively the highest value as $1.405\pm0.020,\;0.623\pm0.040,\;1.422\pm0.022\;{\mu}mol{\cdot}g\;fr\;wt^{-1}{\cdot}h^{-1}\;at\;100\;{\mu}mol\;m^{-2}s^{-1},$ red light, $20^{\circ}C$ and exhibited significant difference among the examined conditions (p<0.001). Germling growth of E. compressa also showed saturation kinetics, and $V_{max}$ and its $K_s$ value at $20^{\circ}C,\;100\;{\mu}mol\;m^{-2}s^{-1},$ 12:12 h were $56.18\%\;day^{-1}$ and 0.33 ${\mu}M$, respectively. SGR (specific growth rate) recorded a maximal value as 49.33-54.80, 39.07-50.72, $47.20-54.53\%\;dat^{-1}$ at $120\;{\mu}mol\;m^{-2}s^{-1},$ blue light and $18^{\circ}C$ respectively, and showed significant difference (p<0.001). Red light made the effective nitrate uptake, but germling growth was largely limited by the light. In fatty acids analysis, PUFAs (polyunsaturated fatty acids) were high at blue light, $18^{\circ}C,\;100\;{\mu}M\;NO_3^-.$ However, irradiance did not affect the production of PUFAs. In conclusion, nitrate uptake and germling growth of E. compressa showed saturation kinetics to external nitrate concentration, and were significantly affected by irradiance, wave length and temperature. Fatty acid composition was also influenced by the factors except for irradiance. Their maximal values, together with the highest production of PUFAs, were found at blue light band, $20^{\circ}C,\;100\;{\mu}mol\;m^{-2}s^{-1},\;and\;100\;{\mu}M\;NO_3^-.$

Production, Isolation, and Purification of L-Asparaginase from Pseudomonas Aeruginosa 50071 Using Solid-state Fermentation

  • El-Bessoumy, Ashraf A.;Sarhan, Mohamed;Mansour, Jehan
    • BMB Reports
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    • 제37권4호
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    • pp.387-393
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    • 2004
  • The L-asparaginase (E. C. 3. 5. 1. 1) enzyme was purified to homogeneity from Pseudomonas aeruginosa 50071 cells that were grown on solid-state fermentation. Different purification steps (including ammonium sulfate fractionation followed by separation on Sephadex G-100 gel filtration and CM-Sephadex C50) were applied to the crude culture filtrate to obtain a pure enzyme preparation. The enzyme was purified 106-fold and showed a final specific activity of 1900 IU/mg with a 43% yield. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the purified enzyme revealed it was one peptide chain with $M_r$ of 160 kDa. A Lineweaver-Burk analysis showed a $K_m$ value of 0.147 mM and $V_{max}$ of 35.7 IU. The enzyme showed maximum activity at pH 9 when incubated at $37^{\circ}C$ for 30 min. The amino acid composition of the purified enzyme was also determined.

8-Fluorociprofloxacin과 Ciprofloxacin의 시험관내 및 생체내 항균효과와 약물동태의 비교 (In vitro and in vivo Antibacterial Activities and Pharmacokinetics of 8-Fluorociprofloxacin and Ciprofloxacin)

  • 최경업;정용환;김제학
    • 약학회지
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    • 제37권3호
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    • pp.235-242
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    • 1993
  • 8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $\mu\textrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $\mu\textrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2\beta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($\pm$SD) $C_{max}$ after i.v. administration were 11.6$\pm$1.6 $\mu\textrm{g}$/ml for 8-FCP, and 10.2$\pm$1.3 $\mu\textrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$\pm$1.8 $\mu\textrm{g}$/ml for 8-FCP and 1.1$\pm$0.9 $\mu\textrm{g}$/ml for CP, respectively. The t$_{1/2\beta}$ was 67.9$\pm$8.4 min for 8-FCP, and 76.4$\pm$7.2 min for CP. The F was 88.6$\pm$6.3% for 8-FCP, and 40.7$\pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

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