• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.385-393
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• 1998

Human neutrophil elastase (HNElastase, EC 3.4.21.37), a causative factor of inflammatory diseases, was purified by Ultrogel AcA54 gel filtration and CM-Sephadex ion exchange chromatography. HNElastase was inhibited by phenylbutazone in a concentration dependent manner up to 0.4 mM, but as the concentration increased, the inhibitory effect gradually diminished. Binding of phenylbutazone to the human neutrophil elastase caused strong Raman shifts at 200, 440, and 1194 $cm^{-1}$. The peak at 1194 $cm^{-1}$ might be evidence of the presence $of\;-N=N-{\Phi}$ radical. The core area of the elastase, according to the visual molecular model of human neutrophil elastase, was structurally stable. A deeply situated active center was at the core area surrounded by hydrophobic amino acids. Directly neighboring the active site was one positively charged atom and two atoms carrying a negative charge, which enabled the enzyme and the drug to form a strong interaction. Phenylbutazone may form a binding, similar to a key & lock system to the atoms carrying opposite charges near the active site of the enzyme molecule. Furthermore, the hydrophobicity of the surrounding amino acid near the active site seemed to enhance the binding strength of phenylbutazone. Binding of phenylbutazone near the active site may cause masking of the active site, preventing the substrate from approaching the active site and inhibiting elastase activity.

• 약학회지
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• 제24권2호
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• pp.97-100
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• 1980

To determine in vitro effects of phenylbutazone and niflumic acid on warfarin binding to rabbit serum protein, warfarin was added to the rabbit plasma, and the bound fraction was determined by warfarin-protein complex fluorescence. The bound fraction was decreased by phenylbtazone and niflumic acid. From this effect niflumic acid was found to have the more potent ability to displace warfarin from protein binding sites than phenylbutazone.

• Journal of Pharmaceutical Investigation
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• 제10권1호
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• pp.24-33
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• 1980

Drug product design of phenylbutazone tablets by direct compressing was investigated. Weight variation, hardness, friability, disintegration time, apparent volume and dissolution rate for experimental tablets of nine formulations which were considered to be the effect of the additive concentration were measured. It was found out that direct compressing by the formulation No. 5 was the most suitable condition (phenylbutazone 16.7%, lactose 25%, calcium phosphate dibasic 15%, $Avicel^{\circledR}$ 41.83% and magnesium stearate 1.5%). The coefficient of correlation between disintegration time and dissolution rate, r, was = -0.97 (P<0.01).

• Toxicological Research
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• 제22권2호
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• 약학회지
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• 제29권3호
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• pp.124-129
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• 1985

A dissolution characteristics of phenylbutazone deposited on Avicel and dibasic calcium phosphate by solvent deposition method were studied. The solvent deposition was confirmed by scanning electron microscopy. Avicel was superior to dibasic calcium phosphate as excipient in dissolution rate. Total amount of phenylbutazone dissolved from Avicel deposition system at 30minutes were enhanced 1.2-1.6 times compared with physical mixtures of them. The dissolution rate of 10% solvent deposition system was highest and that of 75% solvent deposition system was lowest in Avicel system and dibasic calcium phosphate system. Dissolution profile of commercial products was dependent on manufacturing conditions and dissolution rate of 10% Avicel system was greater than that of commercial products.

• Journal of Pharmaceutical Investigation
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• 제5권4호
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• pp.17-23
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• 1975

복용량이 비교적 적고, 난용성 의약품(醫藥品)으로 antirheumatism에 사용되고 있는 phenylbutazone을 macromolecule polymer로서 water soluble carrier인 polyvinylpyrrolidone과 solvent method로 1:1, 1:5, 및 1:9(w/w)의 coprecipitate를 형성(形成)시켰으며, 이들 coprecipitate의 용출 속도를 Pure drug 및 coprecipitate 형성 용매인methanol에서 재결정한 recrystallized pure drug의 그것과 측정 비교(比較)하였다. 1:1,1:5 및 1:9(w/w)의 coprecipitate는 recrystallized pure phenylbutazone보다 약 4.5배의 용출의 증가를 보였고, 이들 1:1,1:5,1:9(w/w)에서의 그 carrier의 양(量)에 따른 용출에의 영향은 거의 없었다. 시간(時間)에 대(對)한 log probit를 plot하여 구(求)한 dissolution half life, $T_{50%}$는 coprecipitate ratio 1:1(w/w)에서는 5.5분, 1:5에서는 10분, 1:9에서는 12.5분이었다.

• Archives of Pharmacal Research
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• 제8권2호
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• pp.59-65
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• 1985

Besides (-) pimara-8(14), 15-dien-19-oic acid [I] which had already been isolated as an active anti-inflammtory principle of Aralia continentalis, (-) kaur-16-en-19-oic acid [II] was separated as another active component of the plant, by tracing albumin stabilizing activity. $IC_{50}$ of [II] for the protein stabilizing activity was 0.026mg/3ml, when those of [I] and phenylbutazone were 0.032 and 0.32 mg/3ml, respectively. Being investigated employing carrageenin-induced edema test in rat hind paw, the anti-inflammatory activity of [II] administered s. c. was slightly lower than that of phenylbutazone, whereas the activity of [II] administered p. p. was three times greater than that of phenylbutazone. These results of [II] were contrary to those of [I] in the aspect of administration routes.

• 약학회지
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• 제23권2호
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• pp.119-124
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• 1979

Eight derivatives of arylpropionic acid, arylcarbonylpropicnic acid, and arylhydroxybutyric acid were synthesized and their structures were elucidated on the basis of elemental analysis and spectral data. Also their antiinflammatory activities were evaluated by the method of the inhibitory effect on the carrageenin-induced rat paw edema and compared with phenylbutazone. Compound (I) exhibited 59% edema inhibition vs control when 100 mg/kg, was orally administered, whereas phenylbutazone showed 57.8% for 50mg/kg.

• 약학회지
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• 제21권4호
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• pp.173-176
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• 1977

Four compounds, benzamide, N-(3-trifluoromethylphenyl) benzamide, N-(2,3-dimethylphenyl) cinnamamide and N-(3-trifluoromethylphenyl) cinnamamide, were synthesized and evaluated their activity by the method of the inhibitory effect on the carrageenin-induced rat paw edema, compared with phenylbutazone. All of these exhibited anti-inflammatory activity, and N-(2,3-dimethylphenyl) benzamide exhibited 45.7% edgema inhibition vs. control when 100mg/kg of dosage was administered, whereas phenylbutazone, 51.4% for 50mg/kg.

• 대한화학회지
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• 제55권4호
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• pp.612-619
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• 2011

1,2-diphenyl-4-butyl-3,5-pyrazolidinedione(phenylbutazone, PB)의 란탄(III) 착물을 합성하여 원소분석, 몰전기전도도 측정, IR, UV-Vis. 및 NMR 스펙트럼으로 특성을 조사하였다. 스펙트럼 데이터로부터 PB가 pyrazolidinedione 고리의 두 카르보닐 산소를 통해 이배위 및 일이온화 리간드로 배위됨을 규명하였다. 몰전기전도도 데이터로부터 이들 착물이 비전해질임을 규명하였다. 이들 착물의 열적 행동을 공기 중에서 TG 및 DTG로 연구한 결과, 탈수화, 열적 안전성 및 열분해에 관한 정보를 얻을 수 있었다. 최종 생성물은 해당 금속의 산화물로 밝혀졌다. 탈수화 및 분해 단계에 대한 열역학 및 반응속도 파라메터를 구하였다. 분해 단계에 대한 음의 엔트로피 값은 반응물보다 활성화 착물이 더 질서있는 구조를 갖는다는 것을 의미하며, 이때 반응은 정상보다 느렸다. 이러한 연구를 바탕으로 착물의 분자식이 $[Ln(PB)_3]{\cdot}5H_2O$(Ln=La 및 Ce) 그리고 $[Ln(PB)_3 (H_2O)_2]{\cdot}2H_2O$(Ln=Pr, Nd 및 Sm)임을 규명하였다.