• 한방안이비인후피부과학회지
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• 제15권2호
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• pp.33-52
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• 2002

The effects of Arctii fructus extract on allegenic inflammation were investigated using in vivo and in vitro test models. Firstly, the cytotoxicity of Arctii fructus extract was validated using MTT assay. As a result, Arctii fructus extract showed no cytotoxic potential, while SDS, a positive control, revealed strong cytotoxic effect. In LLNA assay, Arctii fructus extract showed no skin allergenicity. Next, the anti-allergic actions of Arctii fructus extract were evaluated using rodent experimental models. The oral, intraperitoneal and intradermal administration of Arctii fructus extract significantly inhibited the compound 48／80-induced vascular permeability documented by Evans blue extravasation. In addition, Arctii fructus extract showed potent inhibitory effect on passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, Arctii fructus extract revealed to possess inhibitory potential on the compound 48／80-induced histamine release from rat peritoneal mast cells. Moreover, Arctii fructus extract inhibited the IL-4 and TNF-${\alpha}$ mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Finally, it revealed that Arctii fructus extract significantly suppressed histamin-provoked antigenic inflammation reactions in human prick test. Taken together, these results suggest that anti-allergic action of Arctii fructus extract may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.

• ALGAE
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• 제29권4호
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• pp.333-341
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• 2014

In this study, four compounds isolated from the red alga Laurencia snackeyi were evaluated for their potential anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These compounds were tested for their inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. Since $5{\beta}$-hydroxypalisadin B showed the best activity it was further tested for the production of prostaglandin-$E_2$ ($PGE_2$), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the release of pro-inflammatory cytokines tumor necrotic factor-alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). $5{\beta}$-Hydroxypalisadin B significantly reduced the $PGE_2$ release and suppressed the iNOS and COX-2 expression in LPS-stimulated RAW 264.7 cells. It also significantly reduced the release of pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These findings provide the first evidence of anti-inflammatory potential of $5{\beta}$-hydroxypalisadin B isolated from the red alga L. snackeyi and hence, it could be exploited as an active ingredient in pharmaceutical, nutraceutical and functional food applications.

• 동의생리병리학회지
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• 제23권4호
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• pp.888-894
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• 2009

It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

• 한국임상수의학회지
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• 제22권3호
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• pp.175-180
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• 2005

본 연구는 개에서 키토산 비드를 이용한 cefadroxil 방출에 영향을 주는 인자, 약물을 함유한 최적의 키토산 비드의 제조, 그리고 키토산 비드로부터 약물의 방출을 평가하는 것이다. 키토산 비드는 tripolyphosphate (TPP)와 이온결합으로 생성되며 비드의 크기는 1 mm 미만이었다. 비드로부터 cefadroxil 방출은 여러 인자에 영항을 받는다. TPP의 pH가 감소할수록 cefadroxil의 비드내 함유량은 증가하지만, 비드로부터 방출량은 감소한다. Cefadroxil의 방출속도은 TPP 농도가 증가할수록 감소한다. 결합시간이 길어지면, 방출량이 감소한다. Cefadroxil을 함유한 키토산 비드를 50 mg/kg 용량으로 건강한 개 4두의 피하에 이식한 결과, cefadroxil의 혈청내 농도는 1 ${\mu}g/ml$ 이상으로 7일간 유지되었다. 따라서 cefadroxil을 함유한 키토산 비드는 개의 농피증 치료에 유용한 것으로 사료되며 약물방출을 통제할 수 있는 약물수송체가 이용될 수 있다고 사료된다.

• 아시안잔디학회지
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• 제24권2호
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• pp.145-148
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• 2010

질소는 색감과 품질을 유지하기 위한 잔디의 성장에 필요한 17가지 필수 영양성분중에 하나이다. 완효성 비료는 일정한 양의 질소 영양성분을 오랜기간 동안 제공하기 위해서 개발이 되었고 모래지반에서 특히 더 잘 용 탈되는 질소의 양을 줄이기 위해서 사용이 된다. 이 실험의 목적은 다양한 완효성 비료가 다른 비율로 시비 되었을때 잔디조성에 어떻게 영향을 미치는 지에 대해서 조사하였다. 총 6가지 질소비료가 실험되었으며 켄터키블루그래스가 파종과 뗏장을 위해 사용이 되었다. 뗏장으로 조성된 실험구가 파종으로 조성된 실험구 보다 182에서 518 g 예지물을 더 생산하였다. 파종으로 조성된 실험구중에서는 밀오거나이트가 가장 많은 뿌리의 건중량을 생산하였다. 파종과 뗏장은 잔디의 성장 기간이 다르기 때문에 예지물의 양과 뿌리의 건중량에서 차이가 난다. 본 실험의 결과에 따르면 밀오거나이트가 다른 5가지의 질소비료 보다 예지물의 생산이 적었으며 지하부의 성장이다 좋았으므로 켄터키블루그래스가 처음 조성이 될때는 밀오거나이트가 권장이 된다.

• 한국환경농학회지
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• 제28권2호
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• pp.165-170
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• 2009

환원상태가 발달된 담수상태의 토양이나 습지생태계에서 $NO_3^-$는 환원상태의 진전을 지연시키는 완충역할을 할 수 있다. 논토양에서 $NO_3^-$가 Fe의 환원과 그에 따른 P의 가용화에 미치는 영향을 조사하였다. 담수 후 10 cm 깊이 토양의 산화환원전위 변화는 $NO_3^-$를 처리한 토양과 처리하지 않은 토양에서 현저하게 달리 나타났으며, $NO_3^-$의 환원이 일어나는 동안에는 산화환원전위가 330${\sim}$360 mV 범위에서 유지되었다. 그리고 이 기간 동안 Fe의 환원은 현저히 억제되었다. $NO_3^-$를 처리한 토양 용액의 $PO_4^{3-}$ 함량은 담수 이후 0.2${\sim}$0.3 mg/L 수준 또는 그 이하로 유지되었으며, 반면 $NO_3^-$를 처리하지 않은 경우에는 담수 후 9일째부터 Fe의 환원과 함께 토양 용액의 $PO_4^{3-}$ 함량이 급격히 증가하였다. 일반적인 토양에서 무기태 P의 상당부분이 Fe 산화물에 고정된 형태 및 Fe와 결합된 형태로 존재하므로 Fe의 환원에 따라서 $PO_4^{3-}$가 함께 용출되는 것이다. 이상의 결과를 보면 토양중의 $NO_3^-$가 $Fe^{2+}$와 $PO_4^{3-}$의 용출을 조절하는 요인인 것으로 확인할 수 있다. 토양 용액중의 $NO_3^-$ 농도가 1 mg/L 이상으로 유지되는 상태에서는 토양의 산화환원전위가 330 mV 이하로 낮아지지 못하며, 따라서 Fe의 환원과 그에 따른 P의 용출 또한 현저히 억제되는 것으로 판단된다.

• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.57-71
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• 2004

The objective of this study was to provide a better understanding of SUPAC-IR and its application in handling postapproval changes to immediate release solid oral dosage forms. Originally, SUPAC-IR was aimed at reducing the regulator burdern of the industry when they were making postapproval changes, but still at maintaining the formulation quality and performance of a drug product. The postapproval changes that were covered under SUPAC-IR included variations in the components ad composition of formulation, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. The guidance defined levels of changes, based on the likelihood of risk ocurrence and potential impact of postapproval changes upon the safety and efficacy of a drug product I suggested what a type of fing report should be submitted to the FDA for each level of change. Chemist, manufacturing, and control tests to be executed were also recommended for each change level The important tests specified in the guidance included batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. However, there have been strong demands on revising the current SUPAC-IR in order to resolve some issues and to improve its usefulness in evaluating postapproval changes to immediate release solid oral dosage forms. In particular, the rigorous requirement of case C dissolution test and the definition of batch size were challenged by both academia and the industry. A revision work was in progress to reflect these inputs and to expand the utility of SUPAC-IR. As a result of these concerted efforts, an updated 2nd version of SPAC-IR would be likely to be issued ver soon to the public.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.109-114
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• 2006

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.

• 약학회지
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• 제36권3호
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• pp.212-219
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• 1992

Although oral route is the most convenient route for drug administration, the short and variable transit of drug through GI tract restricts the sustained drug absorption after oral administration. Thus, for sustained absorption of drugs, it is desirable to prolong the GI transit time by retaining the dosage forms in the stomach. In this study, the enzyme-digestible swelling hydrogel was synthesized by heating the mixed solution of N-vinyl-2-pyrrolidone[monomer], acrylated albumin[crosslinking agent] and proxyphylline[drug] at $65^{\circ}C$ for 10 hours in the cylindrical test tube. The resultant hydrogel tablet (diameter; 0.77 cm, thickness; 0.47 cm) was designed to swell in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the drug release. After releasing drug, the hydrogel was expected to be degraded by pepsin, an enzyme in the stomach, and eventually solubilized. Actually, the hydrogel synthesized in the study swelled to a size larger than the diameter of the pylorus ($1.3{\pm}0.7$ cm) and slowly digested in the presence of pepsin. Drug release from the hydrogel was prolonged up to about 12 hours. The swelling kinetics was dependent on albumin acrylation time, drug content and gel thickness. Particularly the gel thickness was the most important factor that influences on drug release. By adjusting these factors, the albumin-crosslinked hydrogel was expected to be retained in the stomach for up to 60 hours and used as a potential platform of drugs for long-term GI absorption.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.248-254
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• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.