• Title/Summary/Keyword: drug design

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Structure-based Drug Design by NMR

  • 전영호;문재웅;김국현;노성구;김진환;강성수;김상수
    • Proceedings of the Korean Magnetic Resonance Society Conference
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    • 1999.02a
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    • pp.6-6
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    • 1999
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Method Development for the Profiling Analysis of Endogenous Metabolites by Accurate-Mass Quadrupole Time-of-Flight(Q-TOF) LC/MS (LC/TOFMS를 이용한 생체시료의 내인성 대사체 분석법 개발)

  • Lee, In-Sun;Kim, Jin-Ho;Cho, Soo-Yeul;Shim, Sun-Bo;Park, Hye-Jin;Lee, Jin-Hee;Lee, Ji-Hyun;Hwang, In-Sun;Kim, Sung-Il;Lee, Jung-Hee;Cho, Su-Yeon;Choi, Don-Woong;Cho, Yang-Ha
    • Journal of Food Hygiene and Safety
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    • v.25 no.4
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    • pp.388-394
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    • 2010
  • Metabolomics aims at the comprehensive, qualitative and quantitative analysis of wide arrays of endogenous metabolites in biological samples. It has shown particular promise in the area of toxicology and drug development, functional genomics, system biology and clinical diagnosis. In this study, analytical technique of MS instrument with high resolution mass measurement, such as time-of-flight (TOF) was validated for the purpose of investigation of amino acids, sugars and fatty acids. Rat urine and serum samples were extracted by selected each solvent (50% acetonitrile, 100% acetonitrile, acetone, methanol, water, ether) extraction method. We determined the optimized liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) system and selected appropriated columns, mobile phases, fragment energy and collision energy, which could search 17 metabolites. The spectral data collected from LC/TOFMS were tested by ANOVA. Obtained with the use of LC/TOFMS technique, our results indicated that (1) MS and MS/MS parameters were optimized and most abundant product ion of each metabolite were selected to be monitorized; (2) with design of experiment analysis, methanol yielded the optimal extraction efficiency. Therefore, the results of this study are expected to be useful in the endogenous metabolite fields according to validated SOP for endogenous amino acids, sugars and fatty acids.

Factors Influencing Performance of MultiDrug-Resistant Organisms Infection Control in Nurses of General Hospital (종합병원 간호사의 다제내성균 감염관리 수행도에 영향을 미치는 요인)

  • Ryu, Jeonglim;Ko, Yu Kyung
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.23 no.2
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    • pp.149-160
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    • 2016
  • Purpose: The purpose of this study was to identify factors influencing performance of MultiDrug-Resistant Organisms (MDROs) infection control by nurses in general hospitals. Methods: The research design was a descriptive survey design using convenience sampling. Data were collected from 130 nurses working in 6 general hospitals. Collected data were analyzed using SPSS/WIN 21.0 program for descriptive statistics, t-test, ANOVA, Pearson correlation coefficients and multiple regression analysis. Results: General hospital nurses' MDROs infection control performance was influenced by their awareness of environmental safety, recognition of MDROs infection control, number of beds in the hospital, whether nurses had nursing experience with infection control and guidelines for MDROs infection control. The most important predictors of MDROs infection control performance were awareness of environmental safety and recognition of MDROs infection control. Conclusion: Findings indicate that it is necessary to include content related to awareness of environmental safety and recognition of infection control in developing MDROs infection control education programs for general hospital nurses.

Pharmacokinetics of Omeprazole-Resin by Crossover Design and the Variation of Absorption upon pH Change in the Guts of the Rat and the Rabbit (Omeprazole 수지염의 흰쥐와 토끼에서의 위장관내 산도변화에 따른 흡수변화 및 교차시험법에 의한 약물동태연구)

  • 권광일;심상호
    • YAKHAK HOEJI
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    • v.39 no.4
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    • pp.401-410
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    • 1995
  • Pharmacolinetic profiles of omeprazole enteric coated granules including Ramezole$^\circledR$, Losec$^\circledR$, omeprazole-Na and omeprazole-resin salt were studied using the crossover design in rats and rabbits. The absorption variance of the preparations at the altered pH condition of the gastrointestinal tract was also studied. After oral administration of four omeprazole enteric coated pellets (10mg/kg) with and without concomitant administration NaHCO$_{3}$ (5 mg/ml, 60 mM) in the rats, the differences of absorplion rate and extent were evaluated. In the NaHCO$_{3}$, administration group, the T$_{max}$ appeared to be 2~10 times shorter than water administration group, and the $C_{max}$ also increased to about 4 times, and the AUC increased to about 2.5 times. Pharmacokinetic parameters of four omeprazole enteric coated pellets in rats showed no statistical significance (ANOVA, P>0.05) in both groups. In the crossover study, the second dosed drug showed 4~5 times increased bioavailability than first dosed drug, which shows the strong carry-over effect of acid secretion of the first dosed drug. The differences of the pharmacokinetic parameters of the two test formulations (Losec$^\circledR$ and omeprazole-resin) showed no statistical significance.

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Research on Thymopentin Loaded Oral N-Trimethyl Chitosan Nanoparticles

  • Yuan, Xiao-Jia;Zhang, Zhi-Rong;Song, Qing-Guo;He, Qin
    • Archives of Pharmacal Research
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    • v.29 no.9
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    • pp.795-799
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    • 2006
  • Peptides, although high efficacy and specificity in their physiological function, usually have low therapeutical activities due to their poor bioavailability when administrated orally. Nanoparticles have been regarded as a useful vector for targeted drug delivery system because they can protect drug from being degraded quickly and pass the gastrointestinal barriers. Here we described a novel oral N-trimethyl chitosan nanoparticles formulation containing thymopentin (Tp5-TMC-NP). N-trimethyl chitosan (TMC) was synthesized and then used to prepare Tp5-TMC-NP by ionotropic gelation. A three-factor, five-level CCD (Central Composite Design) design was used in the optimization procedure, with HPLC as the analyzing method. The resulting Tp5-TMC-NP had a regular spherical surface and a narrow particle size range with a mean diameter of 110.6 nm. The average entrapment efficiency was 78.8%. The lyophilized Tp5-TMC-NP formulation was stable in $4^{\circ}C\;or\;-20^{\circ}C$ after storage of 3 months without obvious changes in morphology, particle size, pH and entrapment ratio. The results of the flow cytometer determination showed that the ratio of $CD4^+/CD8^+$ of Wistar female rat given Tp5-TMC-NP (ig) was 2.59 time that of the group given Tp5 (ig).

Cellular Mechanisms of a New Pyrazinone Compound that Induces Apoptosis in SKOV-3 Cells

  • Wang, Guan;Jiang, Meng-Ying;Meng, Ying;Song, Hong-Rui;Shi, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.797-802
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    • 2014
  • We screened a small molecular library that was designed and independently synthesized in vitro and found a new drug (MY-03-01) that is active against ovarian cancer. We established that MY-03-01 effectively inhibited SKOV-3 cell survival in a dose-dependent manner, based on cell viability rates, and that it not only induced SKOV-3 apoptosis by itself, but also did so synergistically with paclitaxel. Secondly, when MY-03-01 was applied at $40{\mu}M$, its hemolytic activity was less than 10%, compared with the control, and there was almost no damage to nor mal cells at this concentration. In addition, we used DAPI staining and flow cytometry to show that MY-03-01 could significantly induce apoptosis of SKOV-3 cells. Finally, we found that MY-03-01 likely induced SKOV-3 apoptosis by activating caspase3 and caspase9 through the mitochondrial pathway.

Assessing bioequivalence for highly variable drugs based on 3×3 crossover designs (고변동성 제제의 생물학적 동등성 평가에서 3×3 교차설계법 연구)

  • Park, Ji-Ae;Park, Sang-Gue
    • The Korean Journal of Applied Statistics
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    • v.29 no.2
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    • pp.279-289
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    • 2016
  • Bioequivalence trials based on higher order crossover designs have recently been conducted for highly variable drugs since the Ministry of Korea Food and Drug Safety (MFDS) added new regulations in 2013 to widen bioequivalence limits for highly variable drugs. However, a statistical discussion of higher order crossover designs have not been discussed yet. This research proposes the statistical inference of bioequivalence based on $3{\times}3$ crossover design and discusses it with the MFDS regulations. An illustrated example is also given.