• 대한화학회지
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• 제64권2호
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• pp.79-83
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• 2020

A novel pharmacophore with epinastine (1) and NSAID moieties (2-5) was designed by molecular hybridization approach. The hybrid compounds 6-9 were synthesized by EDCI/HOBt or HATU-mediated coupling of 1 with salicylic acid (2), mefenamic acid (3), indomethacin (4) and naproxen (5), respectively, and were assessed for their inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages in vitro. The Hybrids were found to exhibit significant NO production inhibitory effects with half-maximal inhibitory concentration (IC₅₀) values ranging in between 15.96 ± 1.32 and 36.68 ± 2.53 μM and were non-cytotoxic to macrophages. Comparing the inhibition concentration (IC₅₀), cytotoxicity concentration (CC₅₀) and in vitro efficacy index (iEI), 6 (IC₅₀ = 17.97 ± 1.92 μM; iEI = 11.13) and 9 (IC₅₀ = 15.96 ± 1.32 μM; iEI = 12.53) were better suited than other hybrids as well as their parent compound. Our findings signify that hybrids 6 and 9 may serve as platforms for continued investigations for the development of more efficient anti-inflammatory agents.

• Journal of Periodontal and Implant Science
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• 제23권2호
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• pp.243-259
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• 1993

The bone resorbing activity of $PGE_2$ and elevated level of prostaglandins(PGs) and thromboxanes (TXs) in inflamed gingiva which are cyclooxygenase(C) metabolites have been well documented. Nonsteroidal anti-inflammatory drugs(NSAIDs) have been known to suppress gingival inflammation and bone resorption through the specific inhibitory action on the C pathway thereby decrease of various C metabolites. Recent studies provide unequivocal results that gingival tissue metabolizes arachidonic acid(AA) mainly through lipoxygenase(L) pathway. And the results of our previous experiments suggest that indomethacin may have inhibitory action on L as well as C. Thus we started this study to show the influences of several C inhibitors on the L activity at therapeutic and toxic dosage. Periodontal tissue samples were obtained from patients with advanced periodontitis and incubated with $^{14}C-AA(0.2{\mu}Ci)$ and various enzyme inhibitors. The tissue lipid extracts were separated by means of thin layer chromatography(TLC) and analyzed by means of autoradiography and TLC analyzer. Our results showed that aspirin inhibited C more selectively than L, however at higher concentration it also decreased HETEs production significantly. Indomethacin showed dose-dependent inhibition of L as well as C and all of the L metabolites were decreased to the same degree by high concentration of indomethacin. AA-861, which is an experimental tool of selective L inhibitor, showed inhibition of HETEs production but no effect on the production of $TXB_2$, PGs and $LTB_4$. Various propionic acid derivatives NSAIDs(ibuprofen, flurbiprofen, naproxen) showed the same patterns of effect on AA metabolism each other that was profound inhibition of PGs production, to the less degree HETEs and $TXB_2$ production, and of no effect on the $LTB_4$ production.

• Bulletin of the Korean Chemical Society
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• 제27권11호
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• pp.1769-1774
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• 2006

A new liquid chromatographic chiral stationary phase based on (2S,3S)-O,O'-bis-(10-undecenoyl)-N,N'-bis-(3,5-dinitrobenzoyl)-2,3-diamino-1,4-butandiol was prepared starting from (2R,3R)-1,4-bis(benzyloxy)-2,3-butanediol. The new chiral stationary phase was applied to the resolution of racemic anilide derivatives of N-acetyl-a-amino acids, 1,1'-bi-2-naphthol and 3,3'-diaryl-1,1'-bi-2-naphthols. The CSP was also applied to the resolution of some chiral drugs including a diuretic, bendroflumethiazide, and non-steroidal anti-inflammatory agents such naproxen and alminoprofen. In every case, the chiral recognition efficiency of the new CSP was quite excellent.

• 상하수도학회지
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• 제33권5호
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• pp.367-377
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• 2019

In this study, the fate and removal of 15 pharmaceuticals (including stimulants, non-steroidal anti-inflammatory drugs, antibiotics, etc.) in unit processes of a sewage treatment plant (STP) were investigated. Mass loads of pharmaceuticals were 2,598 g/d in the influent, 2,745 g/d in the primary effluent, 143 g/d in the secondary effluent, and 134 g/d in the effluent. The mass loads were reduced by 95% in the biological treatment process, but total phosphorous treatment did not show a significant effect on the removal of most pharmaceuticals. Also, mass balance analysis was performed to evaluate removal characteristics of pharmaceuticals in the biological treatment process. Acetaminophen, caffeine, acetylsalicylic acid, cefradine, and naproxen were efficiently removed in the biological treatment process mainly due to biodegradation. Removal efficiencies of gemfibrozil, ofloxacin, and ciprofloxacin were not high, but their removal was related to sorption onto sludge. This study provides useful information on understanding removal characteristics of pharmaceuticals in unit processes in the STP.

• 정보처리학회논문지:소프트웨어 및 데이터공학
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• 제10권11호
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• pp.465-472
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• 2021

본 논문에서는 약물의 시판 후 이상 반응을 모니터링하기 위해 약물 리뷰 데이터로부터 약물 이상 반응을 탐지할 수 있는 방법을 제시하였다. 부정적인 약물 리뷰는 주로 약물 이상 반응을 언급하고 있다는 점을 고려하여 약물 리뷰들을 감성 분석하여 부정 리뷰를 추출하고, 부정 리뷰에 사전 기반 추출과 개체명 인식 기법을 적용하여 약물 이상 반응을 탐지하였다. 제안하는 BERT+ 알고리즘으로 부정 리뷰를 판별한 다음, MedDRA 표준 의학 용어 사전을 활용해 이상 반응 단어를 찾고, 개체명 인식 기법을 사용하여 구로 표현된 이상 반응 표현을 탐지하였다. 실험을 위해 비스테로이드성 소염진통제 세 종류의 약물 리뷰를 약물 리뷰 사이트로부터 수집하여 테스트하였으며, 실험 결과는 약물 리뷰를 통한 약물 이상 반응 탐지가 현재의 약물 감시 체계의 한계점을 보완할 수 있음을 보여준다.

• Environmental Engineering Research
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• 제22권3호
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• pp.329-338
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• 2017

Nanofiltration (NF) technology is a membrane-based separation process, which has been pervasively used as the high-effective technology for drinking water treatment. In this study, a kind of composite polyamide NF thin film is selected to investigate the removal efficiencies and mechanisms of 14 trace drugs, which are commonly and frequently detected in the drinking water. The results show that the removal efficiencies of most drugs are quite high, indicating the NF is an effective technology to improve the quality of drinking water. The removal efficiencies of carbamazepine, acetaminophen, estradiol, antipyrine and isopropyl-antipyrine in ultrapure water are $78.8{\pm}0.8%$, $16.4{\pm}0.5%$, $65.4{\pm}1.8%$, $71.1{\pm}1.5%$ and $89.8{\pm}0.38%$, respectively. Their rejection rates increase with the increasing of their three-dimensional sizes, which indicates that the steric exclusion plays a significant role in removal of these five drugs. The adsorption of estradiol with the strongest hydrophobicity has been studied, which indicates that adsorption is not negligible in terms of removing this kind of hydrophobic neutral drugs by NF technology. The removal efficiencies of indomethacin, diclofenac, naproxen, ketoprofen, ibuprofen, clofibric acid, sulfamethoxazole, amoxicillin and bezafibrate in ultrapure water are $81{\pm}0.3%$, $86.3{\pm}0.5%$, $85.7{\pm}0.4%$, $93.3{\pm}0.3%$, $86.6{\pm}2.5%$, $90.6{\pm}0.4%$, $59.7{\pm}1.7%$, $80.3{\pm}1.4%$ and $80{\pm}0.5%$, respectively. For these nine drugs, their rejection rates are better than the above five drugs because they are negatively charged in ultrapure water. Meanwhile, the membrane surface presents the negative charge. Therefore, both electrostatic repulsion and steric exclusion are indispensable in removing these negatively charged drugs. This study provides helpful and scientific support of a highly effective water treatment method for removing drugs pollutants from drinking water.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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• pp.437-442
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• 2009

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than $3\;{\mu}M$, diclofenac inhibited reversibly the $Na^+$ current and did irreversibly the L-type $Ca^{2+}$ channels-mediated inward current $(IC_{50}=12.89\pm0.43\;{\mu}M)$ in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type $Ca^{2+}$ currents but not the $Na^+$ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type $Ca^{2+}$ channel, leading to the impairment of E-C coupling in cardiac myocytes.

• 한국임상약학회지
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• 제24권1호
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• pp.15-25
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• 2014

Background: Elderly patients with gastrointestinal (GI) and cardiovascular (CV) risk factors may be more easily exposed to NSAID-related side effects (SEs). Based on the ACG guideline of year 2009, the aim of the study is to evaluate proper use of NSAIDs and gastroprotective drugs according to the degree of GI and CV risk strengths in the patients. Methods: Retrospectively surveyed 410 elderly patients with NSAIDs for more than 30 days at a general hospital in Korea. GI risk factor includes age, ulcer history, high-dose NSIADs, concurrent aspirin use, steroids or anticoagulants. CV risk factor includes angina, myocardial infarction, cerebral infarction, atrial fibrillation or coronary intervention requiring low-dose aspirin. These factors were classified as high/low cardiovascular groups and high/moderate/low GI groups. Results: There were 14 patients in high CV risk group and high GI risk group. The group was recommended not to use NSAIDs as it is not adequate. There were 101 patients in high CV risk group and moderate GI risk group. This group was recommended to use naproxen and PPI/misoprostol. But all patients except one were not adequate. There were 9 patients in low CV risk group and high GI risk group. This group was recommended to use selective COX-2 inhibitor and PPI/misoprostol. 5 cases were proper while 4 cases did not. There were 285 patients in low CV risk and moderate GI risk group who were recommended to use non selective NSAIDs and PPI/misoprostol or selective COX-2 inhibitor only. 103 patients were proper while 182 patients not adequate. Overall, the SEs were higher in those cases for inadequate use of drugs comparing to the adequate. CV SEs were statistically significant. However, SEs for each risk groups were different. For the case of low CV risk group and high/moderate GI risk group, the inadequate use of drugs makes the SE high and the other groups are not. Also, it was not statistically significant. Conclusions: In elderly patients, the inappropriate use of NSAIDs can increase the risk of the disease. Therefore, GI and CV risk must be considered simultaneously, and the proper use of NSAIDs and gastroprotective drugs for each risk groups should be reconsidered.

• 상하수도학회지
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• 제36권2호
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• pp.107-119
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• 2022

The frequent detection and occurrence of micropollutants (MPs) in aquatic ecosystems has raised public health concerns worldwide. In this study, the behavior of 50 MPs was investigated in three different domestic wastewater treatment plants (WWTPs). Furthermore, the Kruskal-Wallis test was used to assess the geographical and seasonal variation of MPs in the WWTPs. The results showed that the concentrations of 43 MPs ranged from less than 0.1 to 237.6 ㎍ L^-1, while other seven MPs including 17-ethynylestradiol, 17-estradiol, sulfathiazole, sulfamethazine, clofibric acid, simvastatin, and lovastatin were not detected in all WWTPs. Among the detected MPs, the pharmaceuticals such as metformin, acetaminophen, naproxen, and caffeine were prominent with maximum concentrations of 133.4, 237.6, 71.5, and 107.7 ㎍ L^-1, respectively. Most perfluorinated compounds and nitrosamines were found at trace levels of 1.2 to 55.3 ng L^-1, while the concentration of corrosion inhibitors, preservatives (parabens), and endocrine disruptors ranged from less than 0.1 to 4310.8 ng L^-1. Regardless of the type of biological treatment process such as MLE, A2O, and MBR, the majority of pharmaceuticals (except lincomycin, diclofenac, iopromide, and carbamazepine), parabens (except Methyl paraben), and endocrine disruptors were removed by more than 80%. However, the removal efficiencies of certain MPs such as atrazine, DEET, perfluorinated compounds (except PFHxA), nitrosamines, and corrosion inhibitors were relatively low or their concentration even increased after treatment. The results of statistical analysis reveal that there is no significant geographical difference in the removal efficacy of MPs, but there are temporal seasonal variations in all WWTPs.

• 분석과학
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• 제21권3호
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• pp.191-200
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• 2008

의약물질(PPCPs)은 수질 환경 시료에서 새로운 오염물질로 대두되고 있다. 본 연구에서는 LC/ESI-MS/MS를 이용하여 환경 수질 시료로부터 7 종(2-퀴노사린카르복시산, 아세틸살리실산, 디클로페낙-소듐, 나프록센, 이부프로펜, 메페남산, 탈니플루메이트)의 산성의약물질을 동시 분석하는 방법을 비교하여 개선하였으며 폐수처리장의 유입수 및 방류수 그리고 연장선상의 하천수의 오염도를 측정하였다. LC/ESI-MS/MS 분석을 위해서 MCX (Mixed Cation eXchange) 카트리지와 HLB (Hydrophilic-Lipophilic Balance) 카트리지를 연결하는 텐뎀 고체상 추출법과 MCX 카트리지만을 사용하는 고체상 추출법을 이용하여 효과적인 시료 정제 및 추출을 수행하였다. 검출한계(LODs)와 방법검출한계(MDLs)는 각각 0.05~1.50 pg/mL, 0.17~4.90 pg/mL 범위를나타내었다. 시료중 1.0 ng/mL 농도(n=3)에서절대회수율은 81.9%~116.3%를 나타내었다. 수질 환경 시료에서 수 pg/mL~ng/mL의 농도로 산성의약물질이 측정되었다.