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    ์ค‘๊ตญ๋ฏธ๋””์–ด์•„ํŠธ์— ๊ด€ํ•œ์—ฐ๊ตฌ:๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์„ ์ค‘์‹ฌ์œผ๋กœ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ํ˜‘๋™๊ณผ์ •๋ฏธ์ˆ ๊ฒฝ์˜, 2014. 8. ์ •ํ˜•๋ฏผ.๋ณธ ๋…ผ๋ฌธ์€ ๋””์ง€ํ„ธ ๋ฏธ๋””์–ด(digital media)๋ฅผ ํ†ตํ•ด ์ค‘๊ตญํ˜„๋Œ€๋ฏธ์ˆ ์˜ ๋™์‹œ๋Œ€์„ฑ๊ณผ ์ง€์—ญ์  ํŠน์ˆ˜์„ฑ์ด๋ผ๋Š” ์ด์ค‘์  ๊ณผ์ œ๋ฅผ ์‹คํ˜„ํ•˜๊ณ  ์žˆ๋Š” ์ค‘๊ตญ ๋ฏธ๋””์–ด ์•„ํ‹ฐ์ŠคํŠธ ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜(็ผชๆ™“ๆ˜ฅ, MiaXiaochun, 1964~)์— ๋Œ€ํ•œ ์—ฐ๊ตฌ์ด๋‹ค. ๊ทธ๋Š” 1990๋…„๋Œ€ ํ›„๋ฐ˜, ์ค‘๊ตญ ์‚ฌํšŒ์˜ ๋ฏธ๋””์–ด ํ™˜๊ฒฝ์ด ์•„๋‚ ๋กœ๊ทธ์—์„œ ๋””์ง€ํ„ธ๋กœ ์ „ํ™˜๋˜๋Š” ์‹œ๊ธฐ์™€ ๋งž๋ฌผ๋ ค ์กฐ๊ฐ์  ํ˜•์‹์„ ์ ‘๋ชฉํ•œ ์‚ฌ์ง„ ์ž‘ํ’ˆ์„ ํ†ตํ•ด ์ƒˆ๋กœ์šด ๋งค์ฒด์˜ ์ธ์‹์„ ๊ฒฝํ—˜ํ•œ ๋’ค, 2005๋…„๋ถ€ํ„ฐ ์„œ๊ตฌ ๊ณ ์ „ํšŒํ™”๋ฅผ ์ฐจ์šฉํ•œ ๋””์ง€ํ„ธ ๋ฏธ๋””์–ด ์ž‘ํ’ˆ์„ ๋ฐœํ‘œํ•ด์™”๋‹ค. 1990๋…„๋Œ€, ๋ณธ๊ฒฉ์ ์œผ๋กœ ์ „๊ฐœ๋˜๋Š” ์ค‘๊ตญ์˜ ๋ฏธ๋””์–ด ์•„ํŠธ๋Š” ์ค‘๊ตญ์˜ ํŠน์ˆ˜ํ•œ ์‚ฌํšŒ์ •์น˜์  ํ™˜๊ฒฝ ์†์—์„œ ํ‘œํ˜„์˜ ์ž์œ ๋ฅผ ์ง€ํ–ฅํ•œ ์ผ๋ถ€ ๊ด€๋… ์˜ˆ์ˆ ๊ฐ€๋“ค์˜ ์ ๊ทน์ ์ธ ๋งค์ฒด์˜ ์ˆ˜์šฉ์„ ์ค‘์‹ฌ์œผ๋กœ ์ด๋ค„์กŒ๋‹ค. ๊ทธ๋“ค์€ ์ค‘๊ตญ ์‚ฌํšŒ์— ๋Œ€ํ•œ ๊ด€๋…์  ํƒœ๋„์™€ ๋‚ด๋ฉด์˜ ์‹ฌ๋ฆฌ์  ๊ท ์—ด์„ ํ‘œํ˜„ํ•˜๋Š”๋ฐ ์žˆ์–ด ํšŒํ™”, ์กฐ๊ฐ ๋“ฑ์˜ ์ „ํ†ต์ ์ธ ์˜ˆ์ˆ  ํ˜•์‹๋ณด๋‹ค ์„ค์น˜, ํ–‰์œ„ ์˜ˆ์ˆ ๊ณผ ๊ฐ™์€ ๋™์‹œ๋Œ€ ๊ฐ€์žฅ ์ „์œ„์ ์ธ ๋ฐฉ์‹์„ ์„ ํ˜ธํ•ด์™”๋‹ค. ์ดˆ๊ธฐ ์ค‘๊ตญ ๋ฏธ๋””์–ด ์•„ํŠธ๋Š” ์ด์™€ ๊ฐ™์€ ์„ค์น˜์™€ ํ–‰์œ„ ์˜ˆ์ˆ ์ด ์ ‘๋ชฉ๋œ ๋น„๋””์˜ค ์•„ํŠธ(vedio art)๋ฅผ ์ค‘์‹ฌ์œผ๋กœ ์ „๊ฐœ๋˜์—ˆ์œผ๋ฉฐ, ๊ธฐ์ˆ ์˜ ๋ฐœ์ „์— ํž˜์ž…์–ด ์ธํ„ฐ๋„ท, ์ปดํ“จํ„ฐ ๋“ฑ ๋‹ค์–‘ํ•œ ๋ฉ€ํ‹ฐ๋ฏธ๋””์–ด๋ฅผ ํ™œ์šฉํ•œ ๋‰ด ๋ฏธ๋””์–ด ์•„ํŠธ๋กœ์˜ ๋ฐœ์ „๊ณผ์ •์„ ๋ณด์—ฌ์ฃผ๊ณ  ์žˆ๋‹ค. ์ค‘๊ตญ์˜ ๋ฏธ๋””์–ด ์•„ํ‹ฐ์ŠคํŠธ๋“ค์€ ๋‹จ์ˆœํžˆ ๊ธฐ์ˆ  ์ค‘์‹ฌ์˜ ํ˜•์‹ ๋…ผ๋ฆฌ์— ์น˜์ค‘ํ•˜์ง€ ์•Š๊ณ , ์ž๊ตญ์˜ ์‚ฌํšŒ๋ฌธํ™”์  ํ™˜๊ฒฝ๊ณผ ๊ทธ ์‚ฌํšŒ๊ตฌ์„ฑ์›๋“ค์˜ ์ •์ฒด์„ฑ, ์„ธ๊ณ„๊ด€์„ ๋ฐ˜์˜ํ•œ ์ž‘ํ’ˆ ์ œ์ž‘์— ๋ชฐ๋‘ํ•ด์™”๋‹ค. ๋ณธ ๋…ผ๋ฌธ์˜ โ…ก์žฅ์—์„œ๋Š” ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์˜ ์ž‘ํ’ˆ ํ˜•์„ฑ ๋ฐฐ๊ฒฝ์œผ๋กœ ์•ž์„œ ์–ธ๊ธ‰ํ•œ ์ค‘๊ตญ ๋ฏธ๋””์–ด ์•„ํŠธ์˜ ํŠน์ง•์ด ๋ฐ˜์˜๋œ ์ฃผ์š” ๋ฏธ๋””์–ด ์ž‘ํ’ˆ๋“ค์„ ์‚ดํŽด๋ณด์•˜๋‹ค. โ…ข์žฅ์—์„œ๋Š” ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์˜ ์ž‘ํ’ˆ์„ ํ˜•์‹๊ณผ ์ฃผ์ œ์ ์ธ ์ธก๋ฉด์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜์—ฌ ๋ถ„์„ํ•ด ๋ณด์•˜๋‹ค. ์ฒซ ์žฅ์—์„œ๋Š” ๊ทธ์˜ ์ž‘ํ’ˆ์— ๊ฐ€์žฅ ํฐ ๊ณจ์กฐ๋ฅผ ์ด๋ฃจ๊ณ  ์žˆ๋Š” ๋””์ง€ํ„ธ ๋ฏธ๋””์–ด์™€ ์ฐจ์šฉ์ด๋ผ๋Š” ํ˜•์‹์  ๋ฐฉ๋ฒ•๋ก ์ด ์ฃผ์ œ๋ฅผ ๊ตฌํ˜„ํ•˜๋Š”๋ฐ ์žˆ์–ด ์ƒํ˜ธ์ž‘์šฉํ•˜๋Š” ํŠน์ง•์„ ๋ฐœ๊ฒฌํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. 3D ํ”„๋กœ๊ทธ๋žจ์„ ํ†ตํ•ด ๊ตฌํ˜„๋œ ์‚ฌ์ด๋ฒ„์ŠคํŽ˜์ด์Šค์—์„œ ์„œ๊ตฌ์˜ ๊ณ ์ „ํšŒํ™”๊ฐ€ ์žฌํ•ด์„ ๋˜๋Š” ๊ณผ์ •์€ ๊ฐ์ƒ์ž๋กœ ํ•˜์—ฌ๊ธˆ ์ƒˆ๋กœ์šด ์‹œ๊ณต๊ฐ„์— ๋Œ€ํ•œ ์ฒดํ—˜์„ ๊ฐ€๋Šฅํ•˜๊ฒŒ ํ•œ๋‹ค. ๋˜ํ•œ ์„œ๊ตฌ์˜ ๊ณ ์ „ํšŒํ™”๋ฅผ ๋“ฑ์žฅํ•˜๋Š” ์ธ๋ฌผ๋“ค์€ ์ž‘๊ฐ€ ์ž์‹ ์˜ ๋ชธ์„ ํ‹€๋กœ ์‚ฌ์šฉํ•˜์—ฌ ์ œ์ž‘๋œ ๋””์ง€ํ„ธ ์ธ์ฒด ์กฐ๊ฐ์œผ๋กœ ์น˜ํ™˜๋˜๋Š”๋ฐ, ์ž‘ํ’ˆ์— ์ฃผ๊ฐ€ ๋˜๋Š” ์‹ ์ฒด ์ด๋ฏธ์ง€๋Š” ์›์ž‘์— ๋ฐ˜์˜๋œ ์„œ๊ตฌ์˜ ์„ธ๊ณ„๊ด€์„ ํ•ด์ฒดํ•˜๋Š” ๊ฒฐ์ •์  ๋„๊ตฌ๋กœ ํ™œ์šฉ๋œ๋‹ค. ๋งˆ์ง€๋ง‰์œผ๋กœ ์„œ๊ตฌ ๊ณ ์ „ํšŒํ™”์˜ ์›๊ทผ๋ฒ•, ์‚ฌ์‹ค์ ์ธ ๋ฌ˜์‚ฌ์™€ ๊ฐ™์€ ํ˜•์‹์  ์š”์†Œ๋“ค์ด ๋””์ง€ํ„ธ ๋ฏธ๋””์–ด์™€ ์ ‘๋ชฉ๋˜์–ด ์ด๋™์‹œ์ (็งปๅ‹•่ฆ–้ปž)์ด๋‚˜ ๊ธฐ์šด์ƒ๋™(ๆฐฃ้Ÿป็”Ÿๅ‹•)๊ณผ ๊ฐ™์€ ์ค‘๊ตญ์˜ ์ „ํ†ต์  ํšŒํ™” ํ˜•์‹์œผ๋กœ ์žฌํ•ด์„๋˜๋Š” ๊ณผ์ •์„ ์ดํ•ดํ•ด ๋ณด์•˜๋‹ค. ๋‘ ๋ฒˆ์งธ ์žฅ์—์„œ๋Š” ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์˜ ์ฃผ์š” ๋ฏธ๋””์–ด ์ž‘ํ’ˆ์„ ๋‚ด์šฉ์ ์ธ ์ธก๋ฉด์œผ๋กœ ์ ‘๊ทผํ•ด ๋ณด์•˜๋‹ค. ๊ทธ์˜ ์ฃผ์š”์ž‘ํ’ˆ์œผ๋กœ , , ์„ ๋ถ„์„ํ•˜๋ฉฐ ๊ทธ์˜ ์ž‘ํ’ˆ์ด ์ธ๊ฐ„ ์กด์žฌ์— ๋Œ€ํ•œ ๋ณธ์งˆ์ ์ธ ํƒ๊ตฌ์™€ ์„ธ๊ณ„๊ด€์— ๋Œ€ํ•œ ์ธ์‹, ์ธ๊ฐ„๊ณผ ๋งŒ๋ฌผ์˜ ์ƒ๋ช…์˜ ๊ทผ์›์œผ๋กœ ๋ฌผ์„ ์ƒ์ง•์ ์œผ๋กœ ํ‘œํ˜„ํ•˜๊ณ  ๊ณผ๊ฑฐ ์„œ๊ตฌ์˜ ์„ธ๊ณ„๊ด€์„ ์˜ค๋Š˜๋‚ ์˜ ํ˜„์‹ค์ ์ธ ์„ธ๊ณ„๊ด€์œผ๋กœ ์žฌํ•ด์„ํ•˜๋Š” ๊ฒฝํ–ฅ๋“ค์„ ์‚ดํŽด๋ณด์•˜๋‹ค. ๋ณธ ๋…ผ๋ฌธ์—์„œ ๋ฏธ๋””์–ด ์•„ํŠธ๋ผ๋Š” ํ‚ค์›Œ๋“œ๋Š” ํ…Œํฌ๋†€๋กœ์ง€์˜ ์ˆ˜์šฉ๊ณผ ํ™œ์šฉ์ด๋ผ๋Š” ํ˜•์‹์ ์ธ ์ธก๋ฉด์—๋งŒ ๊ตญํ•œ๋˜์ง€ ์•Š๋Š”๋‹ค. ํŠน์ˆ˜ํ•œ ์‚ฌํšŒ๋ฌธํ™”์  ํ™˜๊ฒฝ์„ ๋ฐ”ํƒ•์œผ๋กœ ํ˜•์„ฑ๋˜๋Š” ๊ฐœ์ธ์˜ ์‹ ์ฒด์ โ€ค์‹ฌ๋ฆฌ์  ๊ฒฝํ—˜์ด ์ž์•„์ •์ฒด์„ฑ์˜ ํƒ๊ตฌ์™€ ์„ธ๊ณ„๊ด€์— ๋Œ€ํ•œ ์ธ์‹์œผ๋กœ ํ™•์žฅ๋˜๋Š” ๊ณผ์ •์—์„œ ์ฃผ์š”ํ•œ ์†Œํ†ต์˜ ๋งค์ฒด๋กœ์จ ํ™œ์šฉ๋˜๋Š” ๋ฏธ๋””์–ด ์•„ํŠธ์˜ ์ƒˆ๋กœ์šด ๊ฐ€๋Šฅ์„ฑ์„ ์ธ์ง€ํ•˜๊ณ ์ž ํ•œ๋‹ค.๋ชฉ ์ฐจ ๊ตญ๋ฌธ์ดˆ๋ก ๋„ํŒ๋ชฉ๋ก โ… . ์„œ๋ก  โ…ก. ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์˜ ์ž‘ํ’ˆ ํ˜•์„ฑ ๋ฐฐ๊ฒฝ 1. ์ค‘๊ตญ ๋ฏธ๋””์–ด ์•„ํŠธ์˜ ์ „๊ฐœ ์–‘์ƒ 2. ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์˜ ๋งค์ฒด์˜ ์ธ์‹ โ…ข. ๋ฏธ์•„์˜ค์ƒค์˜ค์ถ˜์˜ ์ž‘ํ’ˆ ๋ถ„์„ 1. ํ˜•์‹์  ๋ถ„์„ (1) ๋””์ง€ํ„ธ ๋ฏธ๋””์–ด์™€ ์ฐจ์šฉ (2) ํƒˆ ์ด์›๋ก ์  ๊ด€์ ์˜ ์‹ ์ฒด์ด๋ฏธ์ง€ (3) ๋ฏธ๋””์–ด๋ฅผ ํ†ตํ•œ ์ „ํ†ต์˜ ์žฌํ•ด์„ 2. ๋‚ด์šฉ์  ๋ถ„์„ (1) ๊ฐ€์ƒ ์ตœํ›„์˜ ์‹ฌํŒ (2) H2O (3) ์ขŒ์ฒœ๊ด€์ •(ๅๅคฉ่ง‚ไบ•) โ…ฃ. ๊ฒฐ๋ก  ์ฐธ๊ณ ๋ฌธํ—Œ ๋„ํŒ ABSTRACTMaste

    ์‹คํ—˜์  Cryptosporidium parvum ๊ฐ์—ผ์— ๋Œ€ํ•œ ๋งˆ์šฐ์Šค ์žฅ์ ๋ง‰ ๋ฉด์—ญ ๋ฐ˜์‘์— ์žˆ์–ด์„œ ์žฅ์ƒํ”ผ๋‚ด ๋ฆผํ”„๊ตฌ(IEL)์˜ ์—ญํ• 

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    ํ•™์œ„๋…ผ๋ฌธ(๋ฐ•์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์˜ํ•™๊ณผ ์†Œ์•„๊ณผํ•™์ „๊ณต,1997.Docto

    ์ƒˆ๋กœ์šด ์ ํ˜ˆ๊ตฌ์ƒ์„ฑ ์ด‰์ง„์ œ GC1113์˜ ์ •๋งฅ ๋˜๋Š” ํ”ผํ•˜ ํˆฌ์—ฌ์‹œ์˜ ํšจ๊ณผ์™€ ์•ฝ๋™ํ•™์  ํŠน์„ฑ์— ๋Œ€ํ•œ ํƒ์ƒ‰ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ํ˜‘๋™๊ณผ์ •์ž„์ƒ์•ฝ๋ฆฌํ•™์ „๊ณต, 2014. 2. ์‹ ์ƒ๊ตฌ.Introduction: GC1113, a hybrid Fc fused erythropoietin, is a novel erythropoiesis-stimulating agent which is expected to have an extended duration of action. The preclinical data showed that the hemoglobin increase lasted longer following GC1113 administration than it did following the administration of NESPยฎ(Darbepoetin alfa). This study aimed to investigate the pharmacodynamic (PD), pharmacokinetic (PK) characteristics and tolerability profiles of GC1113 in humans after single intravenous (IV) or subcutaneous (SC) administration and to compare the results with those for NESPยฎ. Methods: A dose-block randomized, placebo- and active- controlled, dose-escalation, phase 1 clinical trial was conducted with 96 healthy volunteers. Blood samples were collected before and up to 672 hours after drug administration and the erythropoietin concentration following the GC1113 or NESPยฎ administration was measured by an enzyme-linked immunosorbent assay (ELISA). PK and PD parameters were determined using noncompartmental methods. Tolerability including immunogenicity evaluation was monitored during hospitalization and until the end of the study. Results: The reticulocyte count-time profiles in the IV GC1113 3โ€“5 ฮผg/kg groups were comparable with those of the NESPยฎ 30 ฮผg. After subcutaneous administration of GC1113, reticulocyte count peaked later and decreased more slowly than it did following NESPยฎ administration. For pharmacokinetics, GC1113 showed faster elimination and slower absorption through subcutaneous administration than NESPยฎ. The GC1113 (0.3โ€“5 ฮผg/kg for IV, 1โ€“8 ฮผg/kg SC) was well tolerated in the volunteers, and no immunogenicity was observed. Conclusions: GC1113 showed erythropoietic activity in healthy volunteers. Intravenous GC1113 showed comparable erythropoietic activity to NESPยฎ, and following subcutaneous administration, the reticulocyte count increase lasted longer for GC1113 than for NESPยฎ. GC1113 was tolerated and effective in the studied dose rangethese findings could be applied to further clinical studies with patients.ABSTRACT i CONTENTS iv LIST OF TABLES v LIST OF FIGURES vi LIST OF ABBREVIATIONS AND SYMBOLS viii INTRODUCTION 1 MATERIALS AND METHODS 4 STUDY DESIGN 4 PHARMACODYNAMIC ASSESSMENTS 6 DETERMINING THE ERYTHROPOIETIN CONCENTRATION 7 PHARMACOKINETIC ASSESSMENTS 8 TOLERABILITY 9 RESULTS 10 PHARMACODYNAMIC ANALYSIS 10 PHARMACOKINETIC ANALYSIS 17 TOLERABILITY 27 DISCUSSION 28 REFERENCES 33 ABSTRACT IN KOREAN 37Maste
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