• 제목/요약/키워드: drug exposure

검색결과 414건 처리시간 0.028초

국소 피부 투여를 위한 이트라코나졸 제제의 조성 (Formulations of Itraconazole for Topical Skin Delivery)

  • 이은아;허성근;최명준;정석재;심창구;김대덕
    • Journal of Pharmaceutical Investigation
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    • 제37권3호
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    • pp.167-171
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    • 2007
  • Itraconazole is one of the most potent antifungal agents available in the market today. However, the low bioavailability due to its poor-water solubility calls for an alternative formulation to the current oral type. A topical itra-conazole-containing formulation may be of use for several reasons including the opportunity to reduce adverse events and generate high local tissue levels, more rapid drug delivery, and lower systemic exposure. The purpose of the present study was to investigate the vehicles for topical skin delivery of itraconazole. The effect of formulations on the hairless mouse skin permeation and deposition of itraconazole was determined using Franz diffusion cells at $37^{\circ}C$. Benzyl alcohol in micro-emulsion significantly increased the solubility of itraconazole, thereby increasing the skin permeation rate. However, lipo-some formulation showed the lowest solubility and permeation rate of itraconazole. Although the solubility of itraconazole in hydrogel formulation was lower than that in microemulsion, skin permeation rate was significantly higher probably due to its adhesive property. Therefore, microemulsion-based hydrogel formulation is expected to synergistically increase the skin permeation rate and skin deposition of itraconazole.

Salvianolic acid B ameliorates psoriatic changes in imiquimod-induced psoriasis on BALB/c mice by inhibiting inflammatory and keratin markers via altering phosphatidylinositol-3-kinase/protein kinase B signaling pathway

  • Wang, Shoufan;Zhu, Lihong;Xu, Yihou;Qin, Zongbi;Xu, Aiqin
    • The Korean Journal of Physiology and Pharmacology
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    • 제24권3호
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    • pp.213-221
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    • 2020
  • Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]-22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.

어린이 건강관련 유해물질 연구방향 (Chemical Risk Factors for Children's Health and Research Strategy)

  • 이효민;정기화
    • 한국식품위생안전성학회지
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    • 제23권3호
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    • pp.276-283
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    • 2008
  • 국내 외 선행연구결과에 의한 어린이 출생 전 후 건강에 영향을 미칠 수 있는 주요 유해물질은 inorganic arsenic, BPA, 2,4-D, dichlorvos, methylmercury, PCBs, pesticide, phthalate, PFOA/PFOS, vinyl chloride 등으로서 국내에서도 이들을 포함한 확인 연구가 수행되어져야 할 것이다. 또한 어린이들의 행동발달과 연관된 생활환경에서의 다양한 인체노출이 확인됨에 따라 탁아소, 유치원과 같은 경우 어린이 활동공간을 대상으로 환경모니터링 및 위해관리활동도 병행되어야 할 것이다. 또한 어린이 건강에 영향을 미치는 유해물질을 중심으로 독성평가, 인체영향연구, 환경 및 인체모니터링과 위해평가를 수행하므로 유해물질의 원인-상관관계를 확인하고 사실자료에 근거한 관리정책을 반영하는 것이 바람직하다.

환경유래 식품오염물질의 우선순위 선정 기법 (Food-CRS-Korea)의 개발과 적용 (Development of Korean Food-Chemical Ranking and Scoring System (Food-CRS-Korea) and Its Application to Prioritizing Food Toxic Chemicals Associated with Environmental Pollutants)

  • 양지연;장지영;김수환;김윤관;이효민;신동천;임영욱
    • Environmental Analysis Health and Toxicology
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    • 제25권1호
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    • pp.41-55
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    • 2010
  • The aims of this study were to develop the suitable "system software" in chemical ranking and scoring (CRS) for the food hazardous chemicals associated with environmental emission and to suggest the priority lists of food contamination by environmental-origined pollutants. Study materials were selected with reference to the priority pollutants list for environment and food management from domestic and foreign research and the number of study materials is 103 pollutants (18 heavy metals, 10 PBTs, 10 EDs, and 65 organic compounds). The Food-CRS-Korea system consisted of the environmental fate model via multimedia, transfer environment to food model, and health risk assessment by contaminated food intake. We have established that health risks of excess cancer risks, hazard quotients (HQs) by chronic toxicity and HQs by reproductive toxicity convert to score, respectively. The creditable scoring system was designed to consider uncertainty of quantitative risk assessment based on VOI (Value-Of-Information). The predictability of the Food-CRS-Korea model was evaluated by comparing the presumable values and the measured ones of the environmental media and foodstuffs. The priority lists based on emissions with background-level-correction are 15 pollutants such as arsenic, cadmium, and etc. The priority lists based on environmental monitoring date are 17 pollutants including DEHP, TCDD, and so on. Consequently, we suggested the priority lists of 13 pollutants by considering the several emission and exposure scenarios. According to the Food-CRS-Korea system, arsenics, cadmium, chromes, DEHP, leads, and nickels have high health risk rates and reliable grades.

폴리락티드-글리콜리드 마이크로스피어에 봉입된 단백질의 항원성 평가 (Antigenicity of Protein Entrapped in Poly(lactide-co-glycolide) Microspheres)

  • 송세현;조성완;신택환;윤미경;최영욱
    • Journal of Pharmaceutical Investigation
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    • 제31권3호
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    • pp.191-196
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    • 2001
  • Biodegradable polymeric microspheres were studied for their usefulness as carriers for the delivery of vaccine antigens. However, protein antigen could be denatured during microencapsulation processes due to the exposure to the organic phase and stress condition of cavitation and shear force. Therefore this study was carried out to re-evaluate the degree of protein denaturation during microencapsulation with poly(lactide-co-glycolide) (PLGA) copolymer. PLGA microspheres containing ovalbumin (OVA), prepared by W/O/W multiple emulsification method, were suspended in pH 7.4 PBS and incubated with shaking at $37.5^{\circ}C$. Drug released medium was collected periodically and analyzed for protein contents by micro-BCA protein assay. In order to evaluate the protein integrity, release medium was subjected to the analyses of SDS-PAGE and size exclusion chromatography (SEC). And enzyme-linked immunosorbent assay (ELISA) was introduced to measure the immunoreactivity of entrapped OVA and to get an insight into the three-dimensional structure of epitope. The structures of entrapped protein were not affected significantly by the results of SDS-PAGE and SEC. However, immunoreactivity of released antigen was varied, revealing the possibility of protein denaturation in some microspheres when it was evaluate by ELISA method. Therefore, in order to express the degree of protein denaturation, antigenicity ratio (AR) was obtained as follows: amount of immunoreactivity of OVA/total amount of OVA released ${\times}100(%)$. ELISA method was an efficient tool to detect a protein denaturation during microencapsulation and the comparison of AR values resulted in more accurate evaluation for immunoreactivity of entrapped protein.

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Synthesis, Characterization and in vitro Anti-Tumoral Evaluation of Erlotinib-PCEC Nanoparticles

  • Barghi, Leila;Asgari, Davoud;Barar, Jaleh;Nakhlband, Aylar;Valizadeh, Hadi
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권23호
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    • pp.10281-10287
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    • 2015
  • Background: Development of a nanosized polymeric delivery system for erlotinib was the main objective of this research. Materials and Methods: Poly caprolactone-polyethylene glycol-polycaprolactone (PCEC) copolymers with different compositions were synthesized via ring opening polymerization. Formation of triblock copolymers was confirmed by HNMR as well as FT-IR. Erlotinib loaded nanoparticles were prepared by means of synthesized copolymers with solvent displacement method. Results: Physicochemical properties of obtained polymeric nanoparticles were dependent on composition of used copolymers. Size of particles was decreased with decreasing the PCL/PEG molar ratio in used copolymers. Encapsulation efficiency of prepared formulations was declined by decreasing their particle size. Drug release behavior from the prepared nanoparticles exhibited a sustained pattern without a burst release. From the release profiles, it can be found that erlotinib release rate from polymeric nanoparticles is decreased by increase of CL/PEG molar ratio of prepared block copolymers. Based on MTT assay results, cell growth inhibition of erlotinib has a dose and time dependent pattern. After 72 hours of exposure, the 50% inhibitory concentration (IC50) of erlotinib hydrochloride was appeared to be $14.8{\mu}M$. Conclusions: From the obtained results, it can be concluded that the prepared PCEC nanoparticles in this study might have the potential to be considered as delivery system for erlotinib.

노박덩굴에 함유된 celastrol 성분의 파킨슨병을 유발시킨 쥐에서의 도파민 신경세포 보호효과 (Protective Effects of Celastrol, the Triterpenoid Component of Celastrus Orbiculatus, on Dopaminergic Neuronal Cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned Parkinson's Disease Rats)

  • 이갑득;김광진;박용기
    • 대한한의학회지
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    • 제29권4호
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    • pp.94-103
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    • 2008
  • Objectives: The aim of this study was to determine whether celastrol, the triterpenoid component of Celastrus orbiculatus, offers neuroprotection against Parkinson's disease (PD) in mice administered 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine(MPTP). Methods: We examined how celastrol affected MPTP-induced neuronal loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in substantia nigra pars compacta (SNpc) in the midbrain of mice. C57BL/6J mice were divided into four groups: (1) saline-saline, (2) saline-celastrol, (3) MPTP-saline, and (4) MPTP-celastrol. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (18mg/kg) at 2 h intervals and then i.p. administered celastrol (3mg/kg) two times at 12 h after last celastrol administration. Expression of TH on the SNpc of brain tissues were analyzed at 7 days after the treatments by immunohistochemistry and Western blot. Results: Immunohistochemical analysis using TH antibody showed that celastrol provided significantly protective effects against MPTP-induced loss of TH-positive dopaminergic neurons in the SNpc region of the midbrain of mice. Our Western blot study also showed that celastrol significantly inhibits the MPTP-induced neuronal damage via the up-regulation of TH protein levels in MPTP mice. Conclusions: The present results suggest that it may be possible to use celastrol for the prevention of nigral degenerative disorders including PD, caused by exposure to toxic substances.

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Reversal of Cisplatin Resistance by Epigallocatechin Gallate Is Mediated by Downregulation of Axl and Tyro 3 Expression in Human Lung Cancer Cells

  • Kim, Kyung-Chan;Lee, ChuHee
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권1호
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    • pp.61-66
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    • 2014
  • Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.

MS EXCEL 및 Bit system을 이용한 피부선량 계산 프로그램의 제작 및 응용 (Production and Application of the Dose Calculation Program which used MS EXCEL and Bit System)

  • 김성철;김종일
    • 대한방사선기술학회지:방사선기술과학
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    • 제32권1호
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    • pp.39-43
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    • 2009
  • 전리방사선을 이용한 의료진단검사는 장치의 발전과 더불어 환자의 삶을 개선시키고 의료검사의 혁명을 가지고 왔다. 하지만 이러한 의료영상의 발전은 대중에 의한 전리방사선피폭의 증가의 원인이 되었다. 이러한 가운데 ICRP에서는 각 국가 및 지역의 실정에 맞게 진단참고준위를 사용하도록 권고하고 있으며, 우리나라에서도 2007년 식품의약품안전청에서 환자선량측정 가이드라인을 제시하였다. 하지만 임상에서는 대부분 선량계가 없어 X선 검사시 환자피부선량을 알 수가 없는 것이 현실이다. 이에 저자는 bit system을 이용하여, PC상에서 엑셀프로그램을 이용하여 간단하게 환자선량을 알 수 있게 프로그램화 하여 그 유용성을 검토하였으며, 그 결과 실측값과 계산값은 약 10% 정도의 차이로 우수한 결과를 나타내었다.

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양악 수술 중 발생한 폐부종의 치험례 (CASE REPORT OF PULMONARY EDEMA DURING TWO JAW SURGERY)

  • 최희원;김경원;이은영;강지연
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제28권2호
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    • pp.178-182
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    • 2006
  • 폐부종은 구강악안면외과 영역의 수술 도중에 발생할 가능성이 있다. 따라서 전신마취하에 수술중인 외과의와 마취의는 환자의 상태를 주의깊게 관찰하여야 하며 수술 중 폐부종이 발생할 가능성에 항상 대비하여야 한다. 폐부종 증세가 발견되는 즉시, 즉각적이고도 적절한 처치를 시행한 경우 예후가 좋으며, 근본적인 원인치료 및 타장기의 합병증 및 후유증에 대하여 검사가 필요하다.