아세트아미노펜 독성평가를 위한 μCCA-μGI 디바이스의 개발

장정윤,Chang Jung-Yun,Shuler Michael L. 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.4

Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(${\mu}CCA-{\mu}GI$) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current ${\mu}CCA$ device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current ${\mu}CCA$ device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration,

원보 : 아세트아미노펜 독성평가를 위한 μCCA-μGI 디바이스의 개발

장정윤 ( Jung Yun Chang ),( Michael L. Shuler ) 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.4

음악과 유아음악 교수자로서의 자신에 대한 예비유아교사의 인식 탐색: 은유 분석을 중심으로

김민정(Min Jung Kim),장정윤(Jung Yun Chang) 전남대학교 교육문제연구소 2023 교육연구 Vol.45 No.3

당뇨병 및 골다공증 치료제의 효율적인 신약개발을 위한 생체표지자 및 대리 결과 변수의 역할 및 활용

성수현,윤휘열,백인환,강원구,장정윤,서경원,권광일,Seong, Soo-Hyeon,Yun, Hwi-Yeol,Baek, In-Hwan,Kang, Won-Ku,Chang, Jung-Yun,Seo, Kyung-Won,Kwon, Kwang-Il 대한약학회 2008 약학회지 Vol.52 No.5

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

의약품 표준품 규격제정 및 제조 : 향균·항생물질의약품의 표준품 제조사업 The preparation of reference standard of antibacterial antibiotics drug

장정윤,장성재,이송득,박승희,정혜윤,민충식,이경희,이정은,우미희 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

황산네틸마이신, 토브라마이신, 오플즉사신, 리팜피신, 황산폴리믹신B의 대한약전 및 식품의약품안전청표준품(KFD.f, reference)을 제조하고자 하였다. 이 물질들을 가지고 FT-lR, TLC, UV를 통하여 확인 및 동정을 하였고, 역가시험으로 액체크로마토그래프법, 미생물학적방법을 시행하여 검토하였고, TLC, HPLC를 디용한 순도시헐과 기타 규격시험을 실시하여 대한약전 및 식품의약품안전청 표준풍을 제조하고 그 규격을 확립하였다. Netilmycin sulfate, tobramycin sulfate, ofloxacin, rifampicin, polymixin B sulfate were tested for the preparation of Korea Pharmacopoeia(KP) and Korea Food and Drug Administration(KFDA) Reference Standards. We purchased the candidate materials and the materials were identified as netilmycin sulfate, tobramycin sulfate, ofloxacin, rifampicin, polymixin B sulfate by FT-IR, TLC and UV. We determined their potencies by HPLC and microbiological method and compared results of two methods. Purity tests were performed by HPLC and TLC. We looked into water content, pH also. On the basis of above results, we made KFDA specification. Materials were authorized as the netilmycin sulfate, tobramycin sulfate, ofloxacin, rifampicin, polymixin B sulfate KFDA Reference Standard for the further distribution.

Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions

Chang, Jung Yun,Oh, Yu-Kyoung,Choi, Han-gon,Kim, Yang Bae,Kim, Chong-Kook 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The timely gelation and retention of in situ-gelling vaginal formulations would be fundamental to improve the effcacy of drugs. In this study, various rheological properties of clotrimazole gels were evaluated for predicting their performance in vagina. Two kinds of thermosensitive and mucoadhesive formulations were composed of poloxamer 407 (P407, 15%), polycarbophil (0.2%), and different amounts of P188 (15 vs, 20%). Both formulations were Newtonian at 20℃ but non-Newtonian at 37℃. Although both liquid formulations gelled below the vaginal temperature, they differed in gelation time and viscoelastic roperties in the presence of vaginal fluid simulant. At body temperature, the formulation with 20% of P188 gelled within 35 s but it took two times longer for the other one gelled. Upon dilution with simulated vaginal fluid, the formulation with 20% of P188 retained the rheology of a gel, but the other one lost the viscoelastic properties typical for a gel. Moreover, after dilution wit simulated vaginal fluid, the elastic moudlus was orders of magnitude higher in the formulations with 20% of P188 relative to the other one. These results indicate that the rheological evalution at the physiologic conditions needs to be preceded to develop more effective in situ-gelling vaginal formulations.

Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system

Kim, Chong-Kook,Hwang, Yong-Yeon,Chang, Jung Yun,Choi, Han-Gon,Lim, Soo-Jeong,Lee, Mi-Kyung 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

Titrated extract of Centella asiatica (TECA), a drug used in treating systemic scleroderma, is poorly water-soluble. Aconventional dosage form for the intramuscular injection of TECA, propylene glycol (PG)-based TECA solution, causes severe pain after intramuscular injection. To improve the solubility of TECA and reduce pain after injection, mixed micellar systems composed of 10% surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline. Ph 7.0(PBS) were prepared. As the ration of Tween 20 to Tween 85 increased form 0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85 from 0:10 to 4:6, followed by an abrupt decrease in size above the ration of 6:4. Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the ration of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the resultant droplet sizes were less than 2 ㎛. No significant changes were observed in the droplet sizes and asiaticoside contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remarkably lower than those of PG-based TECA solution and similar to that of saline solution, irrespective of dilution ratios. Most importantly, they markedy reduced the number of writhes compared with PG-based TECA solution after injection to mice. All of these results suggest that these three TECA micellar formulations prepared with Tween 20 and Tween 85 improved the solubility of TECA and reduced pain following injection, possibly due to the decrease in osmotic pressure. Thus, these micellar formulations composed of optimum ratios of Tween 20 and Tween 85 may have a potential as dosage forms for the intramuscular injection of a poorly water-soluble TECA. ⓒ 2001 Elsevier Science B.V. All rights reserved.

대한약전시험법에 관한 연구(Ⅰ) : 린코마이신의 기기분석법에 관한 연구 Studies on the Instrumental Analysis of Lincomycin

이석호,공학수,김은정,장정윤,최선옥,최리나,이경희 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

대하약저 수재의약품 력석법 기기화의 일환으로 염산린코마이신 및 그 제제를 가지고 고속액 체크로마토그래프법을 이웅하여 부ff하였다. 분석조건은 검출기로는 자외부홉광잘도계t측정파장 : 210nn), 칼람은 μ-Bondapak C_18이동상으로는 1= rhosfhorie acid(13.5-,1009) · CH,CH · He()H 혼합액 (780 : 150 : 150), 유량은 분당 1.0mL의 조작조건으로 분서하였고, 재현섣파 회수율이 양호하게 나타났으며 , 시판품케 적용한 결과 모두 시험기준에 적합하였다.염산린코마이신 및 그 제제의 역가시험땁으로 신속 정확하고 간편한 고속액체크로마토그래프법을 확립하여 장차 공정 시험법으로 이용할 때 기초자료로 찰용할 수 있을 것으로 사료·된다. This study ts an atterupt to determine potencies of lincomycin and its preparatioBs High Performance Liquid Chromatography in comparis,on with microbiological assay. The optimum ana-lrtical conditions were as fotlows; column : f-Bondapalt C,5, detector : UV detector(210nm)』 mobilephase : phosphoric acid(13.5-.1000) · CHfCN · MeO!H (780 : 150 : 150), flow rate : t-OmL/min. injectionvolume : 10#L. The calibration cuue by the UV detector at 210nm was linear within the range of aO~150rg/m1. The results of potencies of lincomycin aTld its preparations by HPLC were similar to those byrnjcrobiotogical assay

세균의 항생제 내성 현황에 대한 모니터링(모니터링 사업) : Monitoring on the Bacterial Resistance to Antibiotics

정혜윤,장성제,공학수,장정윤,최선옥,신행섭,이경희,김광욱,이경원,김은정 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

국내에사 항생제 오남용으로 세균의 항생제 내성률이 세계적으로 높은 수준에 이르러 있는 현재 상팡에서, 병원 환자 및 일반인에서 세균의 내성 전파 현황을 파악하기 위하여 병원 환자 및 일반인에서 분리된 왔색포도상구균에 대하쳐 치료항생제에 대한 내성 현황을 모니러링하였다. 2000년에 3차 의료기관의 환자에서 분리된 황색포도상구균 279균주에 대하여 디스크 확산법에 의하여 항생제 내성를을 조사한 결과, penicillin 내성 띤%, oxacillin 내성 78%, cephalothin 내성 74%, gentaudcin 개성 79%, tetracycline 내성 76%, erythromycin 내성 84%, clindamycin 내성 73%, o뵈oxacin 내성 75%,sulfamethoxazole-Uirnethoprinl (cotrimoxazole) 내성 5%, ohlorarnphenicot 내성 3%, 및 vancomycin 내성 0% 였다. 또한 2000년에 3차 의료기관의 환자에서 분리된 황색포도상구균 107근주에 대하여 최소억제농도 (Hrifmum infibitory concentration, MIC) 측정법에 파라 항생제 내싶률을 조사한 결과, pe굻cillin 내성 59%, oxacillin 내성 80%, erythromycin 내성 실%, tetracycline 내성 76%, gentarlicin 내성 71%, cephalothin 내성 79%, of loxacin 내성 79%, vancomycin 내성 0% 였다. 반면 2000년에 건강할 일반인(498명)(3~71세)의 비강으로부터 분리된 황색포도상구균 130균주 (Baird parker agar배지(Difco)에서 선택적으로 분리 후 황색포도상구균의 확인시헝실시)에 대하여 디 스크 확산법에 따라 치료항생제에 대한 내성를을 측정한 결과 penicillin 내성 95%, oxacillin 내성 2%,cephalothin 내성 1%, gentainicin 내성 11%, tetracycline 내성 긴%, erythromycin 내성 뽀%,cl고damycin 내성 2%, o친oxacin 내성 0%, sulfamethoxazole-trimethoprim 내성 0%, ehlorarn-phenicol 내성 1%, amoxicillin·-clavulanic acid 내성 1%, vancomycin 내싱 0% 였다. 이상의 결과로 부터 지역사회의 일반인으로부터 분리된 황색포도상구균은 penicillin, erythromycin, tetracycline,gentamicin 순으로 내성이 높았던 것으로 나타났다. In the situation of high bacterlal resistance in Korea, to assess diffusion of methicillin-resistant ffoffyforfccus oureus (MRSA) and levels of bacterial resistance toantibiotics in hospital patients and community, we monitored antibiotic resistance of 5. aureusisolates from hospital patients and llealthy volunteers of community. From disc diffusion tesf on279 5. aureus isolates from'hospital patients in 2000, the resistance rates were as follows;penicillin resistant, 99%; of acillin resistant (bfRSA), 78%; cephalothin resistant, 74%; gentamicinresistant, 79%; tetracyclifi3~ refistant, 76%; erythromycin resistant, 84%; clindamycin resistant,73%; of loxacin resisrant, 75%; sulfamethoxazole-trimethoprim (cotrimoxazole) resistant, 6%;ohlorarnphenicol resistant, 3%; vancomIFcin resistant (VRSA), 0%. From minimum inhibitoryconcentrations (MICs) of 107 5. aureus strains from hospital patients in 2000, the resistancerates were as follows; penicillin resistant, 99%, oxacillin resistant (MRSA), 80%; erythromycinresistant, 83%; tetracycline resistant, 76%; gentamicin resistant, 71%, cephalothin resistant, 79%;of loxacin resisrant, 79%; vancomycin resistant (VRSA), 0%. The resistance rates of 5. aureusstrains from hospital patients by disc diffusion and MfC were similar. From disc diffusion 4eston 130 nasal 5. aureus isolats from 498 healthy volunteers of the community, the resistancerates were as follows; penicil;lin resistant, 9j%; oxacillin resistant (MRSA), 2%; erythromycinresistant, 213%; tetracyc)me resistant, 22%; gentamicin resistant, 11%, cephalothin resistant, 1%;clindamycin resistant, 2%, of loTacin resisrant, 0%; sulfamethoxazole-trimethoprim(cotrimoxazole) resistant, 0%; ·Thlorarnphenicol resistant, 1%; amoxicillin-cavulanic acid resistant,1%; yancomycin resistant (VRSA), 0%. Summarily, in the community 2% of nasal 5. aureusisolates were tfRSA, and tht resistance rates of nasal 5. aureus isolates were high in theorder of penicillin (95%), erythrom?cin (f8%), tetracycline (22%), gentamicin (11%).

세균의 항생제 내성 현황에 대한 모니터링(Ⅱ)

정혜윤,이송득,장성재,박승희,장정윤,민충식,신행섭,이경희,김광욱,이동권 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

국내에서 항생제 오남으로 세균의 항생제 내성률이 세계적으로 높은 수준에 이르러 있는 현실에서 일반인에저 세균의 내성 현황을 파악하기 위하여 일반인에서 분리된 황색포도상구균에 대하여 치료항 생제에 대한 내성 현황을 모니터링하였다. 2001년에 전국 6개 도시(서울, 대구, 광주, 제주, 강릉, 청주)의 지역사회 일반인 2835명의 비강으로부터 순수하계 분리된 황석포도상구균 828균주에 대하여 디스크 확산법에 의하여 치교항생제에 대한 내성 현황을 측정한 결과, pe굻cillin 내성 93.7%, frythromycin 내정 3f.7%, tetracycline 내성 16.7%, gentamicin 내성 12,8%, oxacillin 내성 3.5%(29균주), clindamycin 내성 2.4%, chlorampherlicol 내성 1.1%, o리oxacin 내성 0.6%, suffamethoxazolejtrimethoprim 내성 0.1%, vancomycin 내성 0%였다 이들 29개 methicillin-내성 황색포도상구균(MRSA)에서 mecA 유전자를 보윤하는 것을 mecA 유전자 특이 PCR 항법으로 확인하였다 이상의 결과로부터 전국 5개 도시의 지역사회 일반인므로부터 분리된 황색포도상구균은 penicillin, erythromycin, tetracycline, gentamicin 순으로 항생제에 대한 내성이 높았으며, MRSA의 비율은 3.5%이었다 In the situation of high bacterial resistance to antibiotics in Korea, to assess diffusion of methicillin-resistant Staphylococcus aureus(MRSA) and levels of bacterial resistance to antibiotics in community, we monitored antibiotic resistance of S. aureus isolates from healthy volunteers of community. From disc diffusion test on 828 nasal S. aureus isolates from 2835 healthy volunteers of the community of six cities(Seoul, Taegu, Kwangju, Cheju, Kangreung and Chongju) in Korea in 2001, the resistance rates were as follows; penicillin resistant, 93.7%; oxacillin resistant(MRSA), 3.5%(29 isolates); erythromycin resistant, 32.7%; tetracycline resistant, 16.7%; gentamicin resistant, 12.8%; clindamycin resistant, 2.4%; chloramphenicol resistant, 1.1%; ofloxacin resisrant, 0.6%; sulfamethoxazole-trimethoprim(cotrimoxazole) resistant, 0.1%; vancomycin resistant(VRSA), 0% From mecA-specific polymerase chain reaction, the 29 MRSA isolates were identified to contain the mecA gene. Summarily, in the community 3.5% of nasal S. aureus isolates were MRSA, and the resistance rates of nasal S. aureus isolates were high in the order of penicillin(93.7%), erythromycin(32.7%), tetracycline(16.7%) and gentamicin(12.8%).