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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76788
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DC 欄位值語言
dc.contributor.advisor林峯輝(Feng-Huei Lin)
dc.contributor.authorJung-Feng Linen
dc.contributor.author林榮峰zh_TW
dc.date.accessioned2021-07-10T21:36:59Z-
dc.date.available2021-07-10T21:36:59Z-
dc.date.copyright2020-09-23
dc.date.issued2020
dc.date.submitted2020-08-20
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76788-
dc.description.abstract失血是導致與透析有關的鐵缺乏症的主要因素,長期失血將導致缺鐵性貧血。 對於許多患者來說,口服鐵劑是一線治療。元素鐵是一種100% 鐵質來源,可減少每日服藥次數。本研究利用合成的多孔性鐵粒子(Porous Iron Particle, PIP)用於治療缺鐵性貧血的病患。使用改良的硼氫化物還原法成功地合成了多孔鐵顆粒。該方法能夠顯著提高孔徑和表面積,從而增加溶解度。通過Caco-2 細胞模型體外測量其生物利用度,通過監測Caco-2細胞中鐵蛋白的含量來檢查多孔性鐵粒子的體外生物利用度。由於多孔性鐵粒子孔徑提高增加其表面,造成PIP 的鐵蛋白吸收量明顯高於多孔性較差的商業鐵顆粒( p<0.05)。在缺鐵性貧血大鼠中的生物利用度相比,通過測量體重與血紅素相關的參數來檢查多孔性鐵粒子的體內生物利用度。最後,與長期貧血對照組相比,補充多孔性鐵粒子的貧血大鼠的平均血紅蛋白含量和血紅蛋白再生效率明顯更高(p<0.01)。因此,在缺鐵性貧血中,多孔性鐵粒子可以有效恢復血紅素。在為期兩周的口服毒性試驗中,多孔性鐵粒子對大鼠生理學及組織病理學無明顯毒性且不會造成肝臟毒性。因此,在缺鐵性貧血中多孔性鐵粒子可以有效恢復血紅素。zh_TW
dc.description.abstractBlood loss is the main factor leading to iron deficiency related to hemodialysis. Long-term blood loss will lead to iron deficiency anemia. For many patients, oral iron is the first-line treatment. Elemental iron is a 100% iron source that reduces the number of daily medications. In this study, synthetic porous iron particles (PIP) were used to treat patients with iron deficiency anemia. Porous iron particles were successfully synthesized using a modified borohydride reduction method. This method can significantly increase pore size and surface area, thereby increasing solubility. The bioavailability of Caco-2 cell model was measured in vitro, and the in vitro bioavailability of porous iron particles was checked by monitoring the content of ferritin in Caco-2 cells. As the pore size of the porous iron particles increases and the surface is increased, the ferritin absorption of PIP is significantly higher than that of commercial iron particles with poor porosity (p<0.05). Compared with the bioavailability in iron-deficiency anemia rats, the in vivo bioavailability of porous iron particles was examined by measuring the parameters related to body weight and hemoglobin. Finally, compared with the anemia control group, the average hemoglobin content and hemoglobin regeneration efficiency of anemia rats supplemented with porous iron particles were significantly higher (p<0.01). Therefore, in iron-deficiency anemia, porous iron particles can effectively restore hemoglobin. In the two-week oral toxicity test, porous iron particles were not significantly toxic to rat physiology and histopathology and did not cause liver toxicity. Therefore, porous iron particles can effectively restore hemoglobin in iron-deficiency anemia.en
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Previous issue date: 2020
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dc.description.tableofcontents口試委員會審定書 ......................................................... i
誌謝 ............................................................ ii
中文摘要 ............................................................. iii
Abstract ............................................................... iv
CONTENT .............................................................. v
LIST OF FIGURES ....................................................... vii
LIST OF TABLES ........................................................ viii
LIST OF MATH FORMULAS .................................................. ix
ABBREVIATIONS .......................................................... x
Chapter 1 Introduction ................................................. 1
1.1 Anemia of hemodialysis patient ..................................... 1
1.1.1 Iron deficiency Anemia ........................................... 2
1.1.2 Current Treatment in Iron Deficiency Anemia .................... 4
1.2 Object of study .................................................... 7
Chapter 2 Theoretical Basis ............................................ 8
2.1 Chronic kidney disease (CKD) ....................................... 8
2.1.1 Complication ..................................................... 9
2.2 Role of iron ....................................................... 11
2.2.1 Iron absorption in human ......................................... 12
2.3 Preparation of Porous particle ..................................... 13
2.3.1 Porogen........................................................... 14
2.3.2 Dextran .......................................................... 16
Chapter 3 Materials and Methods ........................................ 17
3.1 Materials .......................................................... 17
3.1.1 Chemicals and reagents ........................................... 17
3.1.2 Instruments ...................................................... 19
3.2 Flow chart ......................................................... 20
3.4 Characterization of porous iron particles performance .............. 22
3.4.2 Transmission Electron Microscopy (TEM) ....................... 23
3.4.3 BET .............................................................. 23
3.4.4 Porosity .......................................................... 24
3.4.5 Dynamic Light Scattering (DLS) .................................... 24
3.5 In vitro study ...................................................... 25
3.5.1 Iron Bioavailability in Caco-2 Cell Monolayers ................ 25
3.5.2 Biocompatibility of porous iron particle ............................ 31
3.6 In vivo study ......................................................... 34
3.6.1 Iron Bioavailability in Iron Deficiency Anemia Rats ........ 34
3.6.2 Iron bioavailability and blood parameters ......................... 36
3.6.2 Acute Oral Toxicity............................................... 37
Chapter 4 Results ......................................................... 39
4.1 Characterization of Porous iron particle ............................... 39
4.2 TEM..................................................................... 40
4.3 DLS .................................................................... 41
4.4 Surface area and porosity ........................................... 42
4.5 Biocompatibility of Porous iron particles .............................. 43
4.6 In Vitro study of Caco-2 model ..................................... 44
4.6.1 Immunocytochemistry Staining of Caco-2 monolayer ...... 44
4.6.2 Effect of ferritin concentration on Caco-2 monolayer ....... 45
4.7 In Vivo study of Rat Hemoglobin Repletion Bioassay ................. 46
4.7.1 Effect of hematology values in iron depletion rats ............ 46
4.7.2 The effects of porous iron particles on iron bioavailability......... 47
4.8 In vivo of oral acute toxicity ........................................ 49
4.8.1 Body weight ................................................... 49
4.8.2 Hematology ....................................................... 50
4.8.3 Serum Biochemical ................................................ 51
4.8.4 Hematoxylin Eosin (H E) Staining ............................. 52
Chapter 5 Discussions ................................................. 54
Chapter 6 Conclusion ................................................... 57
REFERENCES ............................................................. 58
dc.language.isoen
dc.subject缺鐵性貧血zh_TW
dc.subject多孔鐵粒子zh_TW
dc.subject口服鐵劑zh_TW
dc.subject透析zh_TW
dc.subject血紅素zh_TW
dc.subjectbioavailabilityen
dc.subjecthemodialysisen
dc.subjectanemiaen
dc.subjectporous iron particlesen
dc.subjecthemoglobinen
dc.title製備與評估以多孔鐵粒子作為口服鐵劑之研究zh_TW
dc.titlePreparation and evaluation of porous iron particles
as oral iron supplement
en
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree博士
dc.contributor.oralexamcommittee陳克紹(Ko-Shao Chen),吳造中(Chau-Chung WU),郭士民(Shyh-Ming Kuo),陳博洲(Po-Chou Chen)
dc.subject.keyword透析,多孔鐵粒子,缺鐵性貧血,口服鐵劑,血紅素,zh_TW
dc.subject.keywordhemodialysis,anemia,porous iron particles,hemoglobin,bioavailability,en
dc.relation.page62
dc.identifier.doi10.6342/NTU202003966
dc.rights.note未授權
dc.date.accepted2020-08-20
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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