• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1995년도 제3회 추계심포지움
• /
• pp.135-136
• /
• 1995

Resent advances in computer technology have introduced a sophisticated capability for computing the biological fate of toxicants in a biological system. This methodology, which has drastically altered risk assessment skill in toxicology, is designed using all the mechanistic information, and all claim better accuracy with extrapolating capability Iron animal to people than conventional pharmacokinetic methods. Biologically based mathematical models in which the specific mechanistic steps governing tissue disposition(pharmacokinetics) and toxic action (pharmacodynamics) of chemicals are constructed in quantitative terms by a set of equations loading to prediction of the outcome of specific toxicological experiments by computer simulation. pharmacokinetic and pharmacodynamic models are useful in risk assessment because their mechanistic biological basis permits the high-to-low dose, route to route and interspecies extrapolation of the tissue disposition and toxic action of chemicals.

• 대한의용생체공학회:의공학회지
• /
• 제9권1호
• /
• pp.73-78
• /
• 1988

The polymer electrolyte complex hydrogels consisting of poly (methacrylic acid) and poly (4-vinylpyrridine) were formed and 5-flurouracil and pilocarpine drugs were loaded on their hydrogels. Cumulative 5-FU released from PEC hydrogel was affected by the degree of loading and release rate of 5-FU was followed by the monolithic type. Cumulative pilocarpine released from PEC hydrogel increased by ionic interaction between cationic pilocarpine and anionic PMA. Release rate showed the zero order after burst effect.

• EDISON SW 활용 경진대회 논문집
• /
• 제4회(2015년)
• /
• pp.212-216
• /
• 2015

Oseltamivir, also known as Tamifu, is an inhibitor of neuraminidase protein which plays an essential role in proliferation and replication of influenza virus. Binding to the active site of neuraminidase, the oseltamivir prevents the protein from enzyme reaction. Conformational change of the protein(neuraminidase) should be accompanied by the enzyme reaction, but the drug inhibits the protein to deform. In this study, we examine the influence of oseltamivir on protein's conformational change in the structural and mechanical point of view. Finite element analysis of the protein can be an useful approach to investigate the influence of oseltamivir on the deformation of a protein. We suggest the finite element based protein model, and then perform the linear static analysis with the displacement loading condition based on the first two largest motion which can be obtained from the normal mode analysis. The results show that it takes more energy to change shape of the protein with an oseltamivir attached than the protein without an oseltamivir.

• 대한화학회지
• /
• 제47권5호
• /
• pp.479-486
• /
• 2003

본 연구에서는 나노입자의 제조 방법인 용매 확산 방법 (emulsification diffusion method)을 이용하여 poly (DL-lactide-co-glycolide) (PLGA) 나노입자를 제조하고 지용성 vitamin A (Retinol)와 Vitamin E acetate를 담지하였다. 고분자 용액은 물에 잘 혼합되는 유기 용매인 에탄올과 아세톤의 이종 혼합 용매를 사용하여 제조하였고 유화제는 생체적합성이 우수한 polyethyleneglycol-polypropyleneglycol diblock copolymer를 사용하였다. 고분자의 농도, 유화제의 농도, 물/오일상의 비, 고분자/약물의 비 등의 인자들이 나노입자의 형성과 약물의 담지 효율에 미치는 영향을 조사하였다. 활성 성분이 로딩된 나노입자를 제조한 후, 입자의 크기와 분포도는 광산란 입도 분석기를 이용하여 측정하였고 담지 효율은 UV-visible spectroscopy를 이용하여 평가하였다. 제조된 나노입자는 50-200 nm의 크기와 단분산 형태의 크기분포를 보였으며 담지 효율은 50-60%까지 얻을 수 있었다. 또한, 유기상과 수용액상에서 이종 혼합 용매와 고분자의 농도에 대한 적당한 조건을 조절함으로써 PLGA 나노입자의 높은 수율과 우수한 물리적 특성을 얻을 수 있었다.

• 한국임상약학회지
• /
• 제15권2호
• /
• pp.105-117
• /
• 2005

Following intracoronary stenting, antiplatelet therapy lead to greater protection from thrombotic complication. A few data are available about the effect of clopidogrel versus cilostazol, an antiplatelet commonly used after intracoronary stenting. To evaluate the efficacy and safety of clopidogrel plus aspirin compared with those of cilostazol plus aspirin in coronary stenting and to evaluate the efficacy of clopidogrel loading dose prior to coronary stealing in clopidogrel group. Data were retrospectively collected from medical charts of patients who had undergone coronary stenting and received either clopidogrel with or without loading 300 mg followed by 75 mg/d (n=58), or 200 mg/d cilostazol(n=72) for 1 year, between January 2000 and May 2002. All patients in both groups received aspirin 200 mg/d throughout the study. The primary endpoints at 7, 30, 180 and 365 days after stealing were the composite of death, Myocardial Infarction, stroke, angina, and revascularization in the intent to treat population and restenosis at follow up angiography. The secondary endpoints were the incidence of bleeding complications at 7, 30, and 365 days, and durg adverse effects at 365 days after stenting. At 180 and 365 days after stenting, the combined primary endpoints were significantly reduced in clopidogrel plus aspirin group (relative risk 0.39; 95% CI 0.17 to 0.92; p=0.021, RR 0.43; 95% CI 0.22 to 0.84; p=0.0085, respectively). However, the combined primary endpoints were not significantly different between the two groups at 7 and 30 days (p:1.00, p=0.79, respectively). Angiographic restenosis rate was 14.3% in clopidogrel plus aspirin uoup and 32.1% in cilostazol plus aspirin group (p=0.19). 300mg of clopidogrel loading dose did not significantly reduce the combined primary endpoints at 30 days after stenting (RR 0.14; 95% CI 0.01 to 2.65; p=0.23). The rate of bleeding complications and drug adverse effects were not different between the two groups. In patients undergoing intracoronary stenting, clopidogrel plus aspirin therapy is more beneficial than cilostazol plus aspirin in reducing major adverse cardiac events with similar rate of bleeding complication. A loading dose of clopidogrel did not lead to a statistically significant reduction in major adverse cardiac events.

• Journal of Pharmaceutical Investigation
• /
• 제33권4호
• /
• pp.319-322
• /
• 2003

Many studies have been attempted to overcome the problems of paclitaxel related to the extremely low aqueous solubility of paclitaxel and the unexpected side-effects caused by $Cremophor^{\circledR}$ EL in a commercial paclitaxel formulation, $Taxol^{\circledR}$. In order to formulate a new delivery system suitable for intravenous administration without toxic excipients, in this study, paclitaxel was incorporated into solid lipid nanoparticles (Px-SLN) by hot homogenization technique using a microfluidizer. Particle size and zeta potential were measured by a Zetasizer. In vitro drug release experiment was performed by a dialysis diffusion method. Each Px-SLN or $Taxol^{\circledR}$ was intravenously administered to the male Sprague-Dawley rats at a dose of 5 mg/kg as paclitaxel. Blood samples were deproteinated with acetonitrile and assayed for paclitaxel by the validated HPLC/MS/MS method. Mean particle size and zeta potential were measured as 72.1 nm (< Polydispersity 0.3) and -41.5 mV, respectively. The content of paclitaxel in SLN was 1.42 mg/ml and the drug loading efficiency was $71.2{\pm}4.3%$. The $AUC_t$ of Px-SLN was 3.4-fold greater than that of $Taxol^{\circledR}$. The Px-SLN might be a promising candidate for an alternative formulation for the parenteral delivery of paclitaxel.

• The Korean Journal of Pain
• /
• 제12권2호
• /
• pp.200-204
• /
• 1999

Background: Patient-controlled analgesia (PCA) has proven to be safe and effective in children from age 5 years, and older and compares favourably with continuous morphine infusion in the older child. We compared fentanyl and butorphanol for opioid use in PCA with ketorolac to determine a suitable drug combination for post-tonsillectomy pain control. Methods: We studied 60 patients, aged 5~12 yrs, undergoing tonsillectomy with or without adenoidectomy under general anesthesia using $N_2O-O_2$-enflurane. Patients were randomly assigned to receive fentanyl $250\;{\mu}g$ (Group 1: n=30) or butorphanol 5 mg (Group 2: n=30) mixed with ketorolac 90 mg and ondansetron 4 mg diluting 100 ml of 5% D/W solutions intravenously via PCA pump after operation. PCA pump were programmed to deliver a 0.05 ml/kg loading dose, 0.01 ml/kg/hr basal infusion, 0.01 ml/kg on demand bolus, 6 min lockout intervals between doses and 4 bolus hourly limit. Total infusion dosage of PCA drug, VAS pain scores, side effects and satisfaction score of both groups were monitored for 48 hrs. Results: Total infusion dosages were fentanyl $170.6\;{\mu}g$ with ketorolac 61.4 mg (Group 1) and butorphanol 2.8 mg with ketorolac 50.4 mg (Group 2). Total infusion dosage, quality of analgesia, side effects and overall satisfaction didn't differ between two groups. Conclusions: Both fentanyl and butorphanol mixed with ketorolac were effective for post-tonsillectomy pain control using PCA pump in children as young as 5 years old.

• Journal of Pharmaceutical Investigation
• /
• 제36권2호
• /
• pp.97-102
• /
• 2006

The aim of this study was to investigate the feasibility and optimize permeability of slim patch type as a transdermal delivery system of caffein. Slim patch type was formulated and tested in modified Franz diffusion cell across cellulose membrane and hairless mouse skin in pH 5.8 phosphate buffer solution (PBS). The effect of $Pharmsolv^{\circledR}$ and drug concentration on permeation at four model, 1,2% $Pharmsolv^{\circledR}$ with $0.12\;mg/cm^2$ caffein and 0.12, $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ through hairless mouse skin was studied in vitro. The release of caffein from slim patch with various loading was fitted by the Higuchi's diffusion equation. The result showed that chemical $Pharmsolv^{\circledR}$ produced a large and significant increase of permeation. The effect of 2% $Pharmsolv^{\circledR}$ on permeation of caffein was greater about 10-fold greater than 1% $Pharmsolv^{\circledR}$ in first 60 minutes. The effect of drug concentration, however, was lower than that produced by chemical $Pharmsolv^{\circledR}$. Within the tested system, the most efficient combination for caffein slim patch type was $0.12\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR},$ although $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ showed highest amounts permeation, because permeated percentages were significantly lower about $1/4{\sim}1/5$ times.

• Journal of Pharmaceutical Investigation
• /
• 제39권6호
• /
• pp.423-429
• /
• 2009

Liposomes have been used as one of the efficient carriers for drug delivery. In this study, anionic liposomes of which surface was modified by using both electrostaic interaction between anionic liposomes and cationically charged BSA molecules at lower pH than isoelectric point (pI) of BSA and denaturation of the BSA-coated liposomes by thermal treatment. The thermally denatured BSA-coated liposomes (DBAL) had mean particle diameter of 125.2${\pm}$1.7 nm and zeta potential value of -22.4${\pm}$4.5 mV. Loading efficiency of model drug, doxorubicin (DOX), into liposomes was 83.0${\pm}$2.6%. Results of in vitro stability study of DBAL in blood plasma showed that the mean particle diameter of DBAL 400 did not increase in blood plasma and adsorption of plasma protein was much less than plain or anionic liposomes. Intracellular uptake of DBAL 400 evaluated by confocal microscopy observation was higher than that of PEG liposomes.

• 폴리머
• /
• 제25권6호
• /
• pp.884-892
• /
• 2001

고혈압 치료제로 사용되는 니페디핀을 지속적으로 방출하는 제형을 제조하기 위하여 poly(L-lactide-co-glycolide) 글리코리드와 랙티드의 몰비 50: 50, 분자량:5000 g/mole)를 이용하여 직접 압축성형 방법으로 생분해성 웨이퍼를 제조하였다. 약물과 고분자의 함량비, 웨이퍼의 두께, 하이드록실 메틸셀룰로오스 (HPMC) 함유량 등을 조절하여 PLGA 웨이퍼를 제조하였고, 이들의 형태학적 특성과 방출거동 및 분해거동을 조사하였다. 제조된 웨이퍼는 11일동안 영차의 안정한 방출거동을 보였고, HPMC를 첨가함으로써 초기 방출거동을 제어하는 등 조건을 달리함으로써 방출거동을 조절할 수 있었다. 수분흡수율과 무게변화를 조사한 결과, 방출 실험 4일부터 웨이퍼의 무게 감소가 현저하게 발생하였고, 방출이 완료된 후에는 무게가 약 40% 감소하였다. 이러한 약물전달 시스템은 압축성형방법에 의해 제조하므로 제조가 간단하고, 약물방출 속도를 정확하게 제어할 수 있으므로 이식을 위한 제형으로 제조시 유용하게 쓰일 것으로 예상되었다.