• Journal of Yeungnam Medical Science
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• 제9권2호
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• pp.396-406
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• 1992

저자들은 Granade와 Artis의 방법에 따라 96-well microplate와 24-well macroplate를 이 용하여 T. rubrum 9주를 대상으로 경구용 항진균제인 ketoconazole과 itraconazole에 대한 MIC를 측정하여 실제 임상사용 가능성을 알아보고 배양온도, 배양용기의 크기, 배지의 종류를 달리하여 MIC에 영향을 줄 수 있는 요소를 점검하여 다음과 같은 결론을 얻었다. 1. 96-well microplate를 사용하여 $25^{\circ}C$에서 배양시 균농도에 따른 판독시기의 차이는 높은 균농도(흡광도 2.0, 1.0)에서는 4일만에, 낮은 균농도(흡광도 0.5, 0.25)에서는 6-8일만에 판독할 수 있었고, MIC는 높은 균농도에서 높았으나 시간이 경과시 점차 차이가 줄어들었다. 2. $37^{\circ}C$와 $25^{\circ}C$에서 각각 배양시 배양온도에 따른 MIC의 차이는 96-well microplate를 사용하여 $37^{\circ}C$에서 배양시 ketoconazole에 대한 MIC는 0.006이하-$0.04{\mu}g/ml$, itraconazole에 대한 MIC는 0.006이하-$0.04{\mu}g/ml$였으며 $25^{\circ}C$에서의 ketoconazole에 대한 MIC는 0.08-$5.68{\mu}g/ml$, itraconazole에 대한 MIC는 0.006-$0.71{\mu}g/ml$로 $37^{\circ}C$에서의 MIC는 $25^{\circ}C$에서의 MIC에 비해 현저히 낮았다. 3. 24-well microplate와 96-well microplate에서 각각 배양시 배양용기의 크기에 따른 판독시기는 96-well microplate 액체배지에서는 4-6일로 24-well macroplate 액체배지에서의 8-12일에 비해 판독시기가 빨랐으나, MIC의 차이는 없었다. 4. 액체배지와 고체배지에서 배양시 배지종류에 따른 MIC의 차이는 액체배지를 함유한 24-well macroplate를 이용한 경우 ketoconazole에 대한 MIC는 0.006이하-$5.68{\mu}g/ml$, itraconazole에 대한 MIC는 0.006 이하-$0.36{\mu}g/ml$였고 고체배지에서는 ketoconazole에 대한 MIC는 0.006이하-$5.68{\mu}g/ml$, itraconazole에 대한 MIC는 0.006 이하-$5.68{\mu}g/ml$로 고체배지에서의 MIC가 다소 높게 측정되었다. 5. 이상의 결과를 종합하여 볼때 96-well microplate를 사용하여, 흡광도 1.0의 균농도로 접종하여, $25^{\circ}C$에서 배양 후 5-6일째 육안으로 판독하는 것이 항진균제 감수성 검사를 빠르고 간편하게 실시 할 수 있는 방법이다.

• Clinical and Experimental Pediatrics
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• 제54권9호
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• pp.385-388
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• 2011

Fungal infections are rarely responsible for arthritis. Few cases of fungal arthritis have been reported, even in immunocompromised hosts susceptible to low-virulence organisms. Herein, the authors report the first case of Candida tropicalis arthritis in a child with a solid tumor. A 13-year-old boy with Ewing's sarcoma developed arthritis in his elbow during the neutropenic period after chemotherapy. Despite treatment with broad-spectrum antibiotics, his condition did not improve and serial blood cultures failed to reveal any causative organisms. After surgical drainage, culture of the joint fluid revealed the presence of C. tropicalis. Itraconazole treatment was started and after 3 months of therapy, the patient completely recovered full elbow function.

• 한국임상수의학회지
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• 제36권2호
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• pp.109-111
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• 2019

A dog with anorexia, cough, and regurgitation was referred to clinic. Diagnostic imaging revealed a solitary mass involving the right cranial and middle lung lobes, compression of the cranial vena cava, and deviation of the heart and mediastinum toward the left side because the mass. The mass was diagnosed as a squamous cell carcinoma via fine needle aspiration. Ten days later, the tumor was larger and the clinical signs were more severe. A combination of piroxicam and itraconazole was administered to control the mass. Two weeks after initiating this treatment, the tumor size decreased and the clinical signs improved significantly.

• Journal of Microbiology and Biotechnology
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• 제14권1호
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• pp.97-104
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• 2004

Water-sludge bacteria were screened to find a lipase enantioselectively hydrolyzing itraconazole precursor, which is well known as the starting material of antifungal drug agents. A bacterial strain was isolated and identified as Acinetobacter junii SY-01. After the strain was cultivated, the enzyme was purified 39.4-fold using ultrafiltration and gel filtration through a Sephadex G-100 chromatographic column and the activity yield was 34.9%. The molecular weight of the enzyme was about 40 kDa, as measured by SDS-PAGE, and the optimum pH was 7.0- 9.0 and stable at pH 6.0- 9.0. The optimum temperature was 45- $5^{\circ}C$, and 73% of the enzymes activity remained after incubation at 70% for 1 h. Enzyme activity was enhanced by gall powder, sodium deoxycholate, a cationic detergent Tween 80, and a non-ionic detergent Triton X-100, but was markedly inhibited by metal ions such as $Hg^{2＋},Cu^{2＋},Ni^{2＋}/,Ca^{2＋}$, and an anionic-surfactant sodium dodecylsulfate. The $K_{m}$ values for (R)- and (S)-enantiomers of the itraconazole precursor were 0.385 and 21.83 mM, respectively, and the $V_{max} values ($\mu$Mㆍmin^{-1}.)$ were 6.73 and 6.49, respectively. The acetyl group among the different acyl moieties of itraconazole precursor showed the highest enantioselectivity for the hydrolysis by the Acinetobacter junii SY-01 lipase, and the lipase from Acinetobacter junii SY-01 displayed better enantioselectivity than that of commercially available lipases and esterases.

• 공업화학
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• 제17권6호
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• pp.633-637
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• 2006

본 연구에서는 triazole계 항진균제인 이트라코나졸의 대량합성을 위한 효과적인 합성법을 제시하였다. Janssen Pharmaceutica에 의해 발표된 기존의 의약화학적 합성경로는 2,4-dichloroacetophenone을 출발물질로 하는 직렬(linear) 합성의 14 단계로서 전체수율이 1.4%에 불과하였고 대량합성에 부적합한 위험물질로서 methanesulfonyl chloride ($CH_{3}SO_{2}Cl$)와 수소기체 및 sodium hydride (NaH)를 사용하고 있다. 또한 고가의 1-acetyl-4-(4-hydroxyphenyl)piperazine 및 팔라듐을 사용함으로써 생산 단가가 높은 문제점이 있었다. 이를 개선하기 위해서 병렬(convergent) 합성 전략을 수립하였는데, 이트라코나졸의 대략 반에 해당하는 중간체 II와 III을 각각 합성한 다음 두 부분을 결합시키는 12단계의 합성공정을 개발하였고 전체 수율은 12.0%로서 합성효율이 크게 개선되었다. 이 과정에서 공정을 간략화하고 위험물질 및 고가의 반응물의 사용을 배제함으로써 생산 원가를 크게 절감시킬 수 있었다.

• Mycobiology
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• 제31권2호
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• pp.95-98
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• 2003

Aantifungal agents were tested against 30 clinical isolates of Cryptococcus neoformans var. neoformans using the NCCLS method(M27-A2). Posaconazole, itraconazole and amphotericin B had lower MIC than the remaining four antifungal agents. The MIC result for posaconazole was over 220-fold lower active than fluconazole. Fluconazole MICs for most isolates fell within the dose-dependant range. The overall MIC ranges and $MIC_{50}s$ were amphotericin B(0.03-0.25; 0.25), fluconazole(0.5-64; 16), itraconazole(0.015-1; 0.125), terbinafine(0.06->2; 1), caspofungin(8-32; 32), voriconazole(0.015-0.5; 0.25), and posaconazole(0.015-0.25; 0.06 ${\mu}g/ml$), respectively. In conclusion, the $MIC_{50}s$ of these drugs did not exhibit any sign of an upward shift with the exception of fluconazole and tendency cross-resistance between the seven drugs was not observed. We conclude that in vitro resistance to antifungal agents has not significantly changed despite the recent wide-spread use of triazoles for long-term treatment of Cryptococcal meningitis.

• 한국임상수의학회지
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• 제31권2호
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• pp.156-158
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• 2014

오타리아 물개의 탈모성 피부염에서 Malassezia spp. 를 분리하였다. Sabouraud dextrose agar에서 성장한 집락형태는 유백색에서 황색조로 변연부는 매끄러웠다. 현미경 검경시 형태는 원형에서 실린더형이었고 증식을 지시하는 budding 형이 관찰되었다. 개의 외이염에서 분리한 Malassezia pachydermatis와 비교하기 위해 26s rRNA 염기서열 분석을 실시하여 99.9% 의 일치도를 보였다. Itraconazole pulse therapy는 매우 효과적이었고 재발하지 않았다. 본 증례는 국내 물개에서 발생한 Malassezia 피부염 최초 보고로 판단된다.

• Journal of Pharmaceutical Investigation
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• 제40권5호
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• pp.305-311
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• 2010

The present study was aimed at preparing microemulsion-based hydrogel (MBH) for the skin delivery of itraconazole. Microemulsion prepared with Transcutol as a surfactant, benzyl alcohol as an oil and the mixture of ethanol and phasphatidyl choline (3:2) as a cosurfactant were characterized by solubility, phase diagram, particle size. MBHs were prepared using 0.7 % of xanthan gum (F1-1) or carbopol 940 (F1-2) as gelling agents and characterized by viscosity studies. The in vitro permeation data obtained by using the Franz diffusion cells and hairless mouse skin showed that the optimized microemulsion (F1) consisting of itraconazole (1% w/w), benzyl alcohol (10% w/w), Transcutol (10% w/w) and the mixture of ethanol and phospahtidylcholine (3:2) (10% w/w) and water (49% w/w) showed significant difference in the flux (${\sim}1{\mu}g/cm^2/h$) with their corresponding MBHs (0.25-0.64 ${\mu}g/cm^2/h$). However, the in vitro skin drug content showed no significant difference between F1 and F1-1, while F1-2 showed significantly low skin drug content. The effect of the amount of drug loading (0.02, 1 and 1.5% w/w) on the optimized MBH (F1-2) showed that the permeation and skin drug content increased with higher drug loading (1.5%). The in vivo study of the optimized MBH (F1-2 with1.5% w/w drug loading) showed that this formulation could be used as a potential topical formulation for itraconazole.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2006년도 제15차 추계학술대회
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• pp.49-50
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• 2006

• Natural Product Sciences
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• 제16권3호
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• pp.175-179
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• 2010

The present study aimed to assess the antifungal properties of the essential oil fraction from Ligusticum chuanxiong (Umbelliferae) and its components against five clinically important Aspergillus species. The essential oil fraction was extracted from the underground parts of the plant by steam distillation, and its main components, namely, Z-ligustilide, butylidene phthalide, and p-cresol were isolated by column chromatography. The antifungal activities of the essential oils were evaluated by the broth dilution method. Both the total essential oil fraction of L. chuanxiong and its components showed significant anti-Aspergillus activity against all five tested strains with MICs between 62.5 and 250 ${\mu}g$/ml, respectively. In a checkerboard microtiter assay, the combination of antibiotics, itraconazole with the essential oil fraction of L. chuanxiong or its main components exhibited synergistic or additive, and in some cases indifferent, effects against the tested Aspergillus species, resulting in FICIs (fractional inhibiting concentration indices) ranging from 0.12 to 2, while the combination of antibiotics, amphothericin B with L. chuanxiong essential oils mostly showed antagonistic effects.