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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林峯輝(Feng-Huei Lin) | |
dc.contributor.author | I-Han Huang | en |
dc.contributor.author | 黃一涵 | zh_TW |
dc.date.accessioned | 2021-06-16T02:34:04Z | - |
dc.date.available | 2025-08-10 | |
dc.date.copyright | 2020-08-10 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-05 | |
dc.identifier.citation | 1. Center for Evidence-Based Medicine, College of Medicine, Taipei Medical University, 2012, Taiwan Osteoporosis Practice Guidelines, New Taipei City, Bureau of Health Promotion, Department of Health, ROC (Taiwan) 2. 林以勤、潘文涵 (2008)。台灣地區19歲以上成人骨密度狀況初探:2007-2008之狀況。衛生福利部辦理之台灣營養健康調查研究 (編號:DOH94-FS-6-4)。臺北市:衛生福利部國民健康署。 3. Brenda Galvan (2014). Curbing osteoporosis by creating strong bones with Pilates exercises. Costa Mesa, CA.:BASI Pilates Studios. 4. Sozen, T., Ozisik, L., Calik Basaran, N. (2017). An overview and management of osteoporosis. European Journal of Rheumatology, 4(1), 46-56. doi:10.5152/eurjrheum.2016.048 5. International Osteoporosis Foundation | Bone Health. (n.d.). Retrieved from https://www.iofbonehealth.org/ 6. Kanis, J. A., Kanis, J. A. (1994). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. Osteoporosis International, 4(6), 368-381. doi:10.1007/bf01622200 7. Johnell, O., Kanis, J. A. (2004). An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporosis International, 15(11), 897-902. doi:10.1007/s00198-004-1627-0 8. Kanis JA (2007) WHO Technical Report, University of Sheffield, UK: 66. 9. Tu, K. N., Lie, J. D., Wan, C., Cameron, M., Austel, A. G., Nguyen, J. K., … Hyun, D. (2018). Osteoporosis: A Review of Treatment Options. P T : a peer-reviewed journal for formulary management, 43(2), 92–104. 10. Kanis, J. A. (2002). Diagnosis of osteoporosis and assessment of fracture risk. The Lancet, 359(9321), 1929-1936. doi:10.1016/s0140-6736(02)08761-5 11. Garnero, P. (2000). Markers of Bone Turnover for the Prediction of Fracture Risk. Osteoporosis International, 11(0), S55–S65. doi:10.1007/s001980070006 12. Peacock, M. (2010). Calcium Metabolism in Health and Disease. Clinical Journal of the American Society of Nephrology, 5(Supplement 1), S23–S30. doi:10.2215/cjn.05910809 13. Harold N Rosen, MD. (2020). Calcium and vitamin D supplementation in osteoporosis. Wolters Kluwer. 14. Sampson, H. W. (2002). Alcohol and other factors affecting osteoporosis risk in women. Alcohol Research and Health, 26(4), 292-298. 15. Kanis, J.A., Johnell, O., Oden, A. et al. Osteoporos Int (2005) 16: 155. doi:10.1007/s00198-004-1640-3 16. Lee, K. Y., Mooney, D. J. (2012). Alginate: Properties and biomedical applications. Progress in Polymer Science, 37(1), 106-126. doi:10.1016/j.progpolymsci.2011.06.003 17. Brown, P. W., Fulmer, M. (1991). Kinetics of Hydroxyapatite Formation at Low Temperature. Journal of the American Ceramic Society, 74(5), 934–940. doi:10.1111/j.1151-2916.1991.tb04324.x 18. Wu, J., Fong, Y., Tsai, H., Chen, Y., Tsuzuki, M., Tang, C. (2008). Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts. European Journal of Pharmacology, 588(2-3), 333-341. doi:10.1016/j.ejphar.2008.04.030 19. Ang, E. S., Yang, X., Chen, H., Liu, Q., Zheng, M. H., Xu, J. (2011). Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL-induced NF-κB and ERK activation. FEBS Letters, 585(17), 2755-2762. doi:10.1016/j.febslet.2011.07.046 20. Şahin, E. (2018). Calcium Phosphate Bone Cements. Cement Based Materials. doi:10.5772/intechopen.74607 21. Nasrollahi, N., Nourian Dehkordi, A., Jamshidizad, A., Chehelgerdi, M. (2019). Preparation of brushite cements with improved properties by adding graphene oxide. International Journal of Nanomedicine, Volume 14, 3785–3797. doi:10.2147/ijn.s196666 22. Wang, L., Nancollas, G. H. (2008). Calcium Orthophosphates: Crystallization and Dissolution. Chemical Reviews, 108(11), 4628–4669. doi:10.1021/cr0782574 23. Brown, P. W. (1992). Phase Relationships in the Ternary System CaO─P2O5─H2O at 25°C. Journal of the American Ceramic Society, 75(1), 17–22. doi:10.1111/j.1151-2916.1992.tb05435.x 24. GINEBRA, M. (2008). Calcium phosphate bone cements. Orthopaedic Bone Cements, 206-230. doi:10.1533/9781845695170.2.206 25. Brown, P. W., Fulmer, M. (1991). Kinetics of Hydroxyapatite Formation at Low Temperature. Journal of the American Ceramic Society, 74(5), 934–940. doi:10.1111/j.1151-2916.1991.tb04324.x 26. Tas, A. C., Bhaduri, S. B. (2004). Chemical Processing of CaHPO4.2H2O:. Its Conversion to Hydroxyapatite. Journal of the American Ceramic Society, 87(12), 2195-2200. doi:10.1111/j.1151-2916.2004.tb07490.x 27. Chang, H. C., Gupta, S. K., Tsay, H. S. (2011). Studies on folk medicinal fern: an example of “Gu-Sui-Bu”. In Working with Ferns (pp. 285-304). Springer, New York, NY. 28. 陳振義, 陳進分, 吳金濱. (2012). 臺東原生藥用植物 [骨碎補] 柚皮苷含量之分析. 作物, 環境與生物資訊, 9(4), 257-264. doi:10.30061/CEB.201212.0005 29. Ko, Y., Wu, J., Ho, H., Lin, W. (2012). Antiosteoporotic activity of Davallia formosana. Journal of Ethnopharmacology, 139(2), 558-565. doi:10.1016/j.jep.2011.11.050 30. Wu, J., Fong, Y., Tsai, H., Chen, Y., Tsuzuki, M., Tang, C. (2008). Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts. European Journal of Pharmacology, 588(2-3), 333-341. doi:10.1016/j.ejphar.2008.04.030 31. Ang, E. S., Yang, X., Chen, H., Liu, Q., Zheng, M. H., Xu, J. (2011). Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL-induced NF-κB and ERK activation. FEBS Letters, 585(17), 2755-2762. doi:10.1016/j.febslet.2011.07.046 32. 張永勳、何玉鈴(2015)。臺灣市售易混淆中藥鑑別圖鑑。臺北市:衛生福利部中醫藥司。 33. Liu, Y., Wu, H., Nie, Y., Chen, J., Su, W., Li, P. (2011). Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-κB pathway. International Immunopharmacology, 11(10), 1606-1612. doi:10.1016/j.intimp.2011.05.022 34. Zhou, C., Lai, Y., Huang, P., Xie, L., Lin, H., Zhou, Z., … Gao, L. (2018). Naringin attenuates alcoholic liver injury by reducing lipid accumulation and oxidative stress. Life Sciences. doi:10.1016/j.lfs.2018.07.031 35. 鄧富元, 龔素芳, 夏毅然, 高文斌, 謝耀東. (2006). NF-κB 在發炎反應, 細胞凋亡與癌症生成過程中的調控. 中華牙醫學雜誌 (中文版), 25(1), 12-24. 36. Jacobs, M. D., Harrison, S. C. (1998). Structure of an IκBα/NF-κB Complex. Cell, 95(6), 749–758. doi:10.1016/s0092-8674(00)81698-0 37. Schuliga, M. (2015). NF-kappaB Signaling in Chronic Inflammatory Airway Disease. Biomolecules, 5(3), 1266-1283. doi:10.3390/biom5031266 38. Peng-Zhang, Dai, K., Yan, S., Yan, W., Chao-Zhang, Chen, D., ... Xu, Z. (2009). Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell. European Journal of Pharmacology, 607(1-3), 1-5. doi:10.1016/j.ejphar.2009.01.035 39. Wu, J., Fong, Y., Tsai, H., Chen, Y., Tsuzuki, M., Tang, C. (2008). Naringin-induced bone morphogenetic protein-2 expression via PI3K, Akt, c-Fos/c-Jun and AP-1 pathway in osteoblasts. European Journal of Pharmacology, 588(2-3), 333-341. doi:10.1016/j.ejphar.2008.04.030 40. Ishikawa, M., Iwamoto, T., Nakamura, T., Doyle, A., Fukumoto, S., Yamada, Y. (2011). Pannexin 3 functions as an ER Ca2+channel, hemichannel, and gap junction to promote osteoblast differentiation. The Journal of Experimental Medicine, 208(7), i21-i21. doi:10.1084/jem2087oia21 41. Feng, W., Liu, H., Luo, T., Liu, D., Du, J., Sun, J., ... Li, M. (2017). Combination of IL-6 and sIL-6R differentially regulate varying levels of RANKL-induced osteoclastogenesis through NF-κB, ERK and JNK signaling pathways. Scientific Reports, 7(1). doi:10.1038/srep41411 42. Ang, E. S., Yang, X., Chen, H., Liu, Q., Zheng, M. H., Xu, J. (2011). Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL-induced NF-κB and ERK activation. FEBS Letters, 585(17), 2755-2762. doi:10.1016/j.febslet.2011.07.046 43. Lee, K. Y., Mooney, D. J. (2012). Alginate: Properties and biomedical applications. Progress in Polymer Science, 37(1), 106–126. doi:10.1016/j.progpolymsci.2011.06.003 44. Ching, S. H., Bansal, N., Bhandari, B. (2015). Alginate gel particles–A review of production techniques and physical properties. Critical Reviews in Food Science and Nutrition, 57(6), 1133-1152. doi:10.1080/10408398.2014.965773 45. Liang, Y., Kashdan, T., Sterner, C., Dombrowski, L., Petrick, I., Kröger, M., Höfer, R. (2015). Algal Biorefineries. Industrial Biorefineries White Biotechnology, 35-90. doi:10.1016/b978-0-444-63453-5.00002-1 46. Leick, S., Henning, S., Degen, P., Suter, D., Rehage, H. (2010). Deformation of liquid-filled calcium alginate capsules in a spinning drop apparatus. Physical Chemistry Chemical Physics, 12(12), 2950. doi:10.1039/b921116k 47. Klein, J., Stock, J., Vorlop, K.-D. (1983). Pore size and properties of spherical Ca-alginate biocatalysts. European Journal of Applied Microbiology and Biotechnology, 18(2), 86–91. doi:10.1007/bf00500829 48. T.L Alford, L.C. Feldman and J.W. Mayer, Fundamentals of Nanoscale Film Analysis, 2007, Springer. doi: 10.1007/978-0-387-29261-8 49. Wells, O. C. (2001). Scanning Electron Microscopy. Encyclopedia of Materials: Science and Technology, 8265–8269. doi:10.1016/b0-08-043152-6/01479-0 50. Uo, M., Wada, T., Sugiyama, T. (2015). Applications of X-ray fluorescence analysis (XRF) to dental and medical specimens. Japanese Dental Science Review, 51(1), 2-9. doi:10.1016/j.jdsr.2014.07.001 51. Misof, B., Roschger, P., Fratzl, P. (2017). 3.26 Imaging Mineralized Tissues in Vertebrates. Comprehensive Biomaterials II, 549–578. doi:10.1016/b978-0-12-803581-8.09827-1 52. Chatterjee, A. K. (2001). X-Ray Diffraction. Handbook of Analytical Techniques in Concrete Science and Technology, 275–332. doi:10.1016/b978-081551437-4.50011-4 53. Cell Proliferation Reagent WST-1 (2018). Roche. 54. Yin, L., Wei, Y., Wang, Y., Xu, Y., Yang, Y. (2013). Long Term and Standard Incubations of WST-1 Reagent Reflect the Same Inhibitory Trend of Cell Viability in Rat Airway Smooth Muscle Cells. International Journal of Medical Sciences, 10(1), 68-72. doi:10.7150/ijms.5256 55. LDH Cytotoxicity Detection Kit (2018). TaKaRa Bio Inc. 56. LIVE/DEAD Viability/Cytotoxicity Kit for mammalian cells (2005). Molecular Probes. 57. Alkaline Phosphatase Activity Colorimetric Assay Kit. BioVision. 58. Langenbach, F., Handschel, J. (2013). Effects of dexamethasone, ascorbic acid and ?-glycerophosphate on the osteogenic differentiation of stem cells in vitro. Stem Cell Research Therapy, 4(5), 117. doi:10.1186/scrt328 59. Bustin, S. A., Benes, V., Garson, J. A., Hellemans, J., Huggett, J., Kubista, M., … Wittwer, C. T. (2009). The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments. Clinical Chemistry, 55(4), 611–622. doi:10.1373/clinchem.2008.112797 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53939 | - |
dc.description.abstract | 骨質疏鬆症是一種罹患機率隨著年齡增加而增加的老年疾病,隨著骨質的流失、骨組織的強度下降,骨折的風險便會持續增加,據統計有1/5的男性與1/3的女性終其一生會罹患此症。 目前對於骨質疏鬆症的治療手段多有其缺陷。因此,本研究欲開發一種新型態的口服藥劑,將透鈣磷石與柚皮苷包覆在褐藻膠中形成微粒以方便吞食,透鈣磷石提供穩定且易於吸收的鈣質來源,柚皮苷則是已被證實能夠提升骨質密度的中藥萃取物。 本研究使用XRD、SEM與EDS來確認透鈣磷石的合成與褐藻膠包覆透鈣磷石和柚皮苷的微粒性質,並且確認其在胃酸的環境(pH = 2)中能夠大量電解並釋放出鈣離子,以增加鈣質在體內的吸收率。體外與體內測試皆分為生物相容性與有效性的測試。在體外測試階段,使用L929細胞確認了本研究使用的材料有著良好的生物相容性,並使用人類骨肉瘤細胞MG-63來進行成骨細胞的成骨活性試驗,發現本研究之褐藻膠微粒萃取液對於促進成骨作用的效果較一般培養液與已知能增加成骨作用活性之成骨培養液佳。因此進一步以大鼠之體內測試加以驗證之。 體內測試以卵巢切除誘發骨質流失並再飼養兩個月以使大鼠骨質疏鬆,並分成卵巢未切除組、切除不處理組與切除給藥組。本研究將微粒磨碎並且以管餵的方式每日餵食大鼠,餵食六周後以X光測量其股骨之骨質密度並且在下一周犧牲。血清生化學與組織切片的結果皆顯示本實驗材料無明顯生物毒性,在有效性測試方面,骨密度測試、無機物比例評估與骨組織切片之結果皆顯示本實驗材料相較於切除不處理組能略為提升骨質;而在血清生化學分析中,可以發現實驗材料組的成骨指標相較於其他組別有大幅的增加,顯示本實驗材料能有效增加成骨作用之速率,以降低骨折風險。 | zh_TW |
dc.description.abstract | Osteoporosis, one of the most prevalent geriatric syndromes, is a disease caused by the loss of bone mass and causing the decreasing of bone strength and the increasing of bone fracture risk. The prevalence rate and fatality rate are proportional to age, which imposes an onerous burden on both society and economic system. Statistically, one-fifth of men and one-third of women will suffer this disease during their lifetime, so it is important to have an effective solution to this “silent killer.” Current treatments for osteoporosis all have some disadvantages such as adverse events, aggravating medication restrictions, and limited efficacy. To find a better solution for osteoporosis, we are going to develop a new oral formula. Two molecules, brushite and naringin, were chosen to increase bone mass. Brushite can stably and considerably release calcium and serves as calcium supplement in this study. Naringin, an extract of traditional Chinese medicine called Gu-Sui-Bu (骨碎補), has a proved effect on reducing the bone fracture risk. Furthermore, the two molecules were encapsulated in alginate hydrogel for patients to easily swallow. XRD, SEM, and EDS analyses indicated the syntheses of brushite and alginate sphere were successful. The solubility of brushite at pH = 2 was ideal for calcium releasing and absorbing. In vitro studies and in vivo studies were both divided into biocompatibility and validity test. For in vitro studies, we followed ISO 10993 to conduct biocompatibility and cytotoxicity test with L929 cells. For validity test, human osteosarcoma cell line MG-63 served as osteoblast to evaluate the osteogenic activity. The outcome indicated that the extract of ANB could significantly increase the osteogenic activity compared with normal medium and osteogenic medium. The animal model of in vivo study was SD rat and osteoporosis was induced by ovariectomy. The rats were divided into three groups, control group, ovariectomy group, and ANB group. After rats were fed by oral gavage for 6 weeks, we measured BMD of rats and sacrificed them on the next week. Serum biochemistry and histological examination indicated that the materials used in this study had ideal biocompatibility and biotoxicity and suitable for lives to intake. BMD test, inorganic matrix assessment, and histological examination indicated that bone mass of ANB group would slightly increase compared with ovariectomy group. Serum biochemistry showed that the concentration of bone formation marker of ANB group was much higher than that in other groups, which indicated that ANB could obviously increase the rate of bone formation. If the body is treated for longer time, ANB can furtherly decrease the risk of fragility fracture. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T02:34:04Z (GMT). No. of bitstreams: 1 U0001-0408202013083300.pdf: 2932672 bytes, checksum: 49ea4b7d4296fd229f7b6bae2127b931 (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 中文摘要 i Abstract ii Table of Contents iv List of Figures vii List of Tables ix List of Formulae x List of Abbreviations xi Chapter I Introduction 1 1.1 Overview of Osteoporosis 1 1.2 Definition, Classifications and Diagnoses of Osteoporosis 2 1.3 Factors Affecting Bone Metabolism 4 1.3.1 Regular Exercise 5 1.3.2 Calcium Supplement 5 1.3.3 Vitamin D3 6 1.3.4 Parathyroid Hormone (PTH) 7 1.3.5 Age 7 1.3.6 Estrogen 7 1.4 Preventions and Treatments 7 1.4.1 Parathyroid Hormone Analogues 8 1.4.2 Hormone Replacement Therapy (HRT) 8 1.4.3 Calcitonin 9 1.4.4 Bisphosphonates 9 1.5 Purpose of Study 11 Chapter Ⅱ Theoretical Foundation 12 2.1 Brushite 12 2.2 Naringin 14 2.2.1 Anti-inflammation of Naringin 15 2.2.2 Effects of Naringin on Osteoblasts 16 2.2.3 Effects of Naringin on Osteoclasts 17 2.3 Alginate Hydrogel 17 Chapter Ⅲ Methodology 20 3.1 Flowchart 20 3.2 Instruments 22 3.3 Reagents and Chemicals 23 3.4 Synthesis of Brushite 25 3.5 Synthesis of ANB (Alginate Encapsulating Naringin and Brushite) 25 3.6 Principles of Material Characteristic Analyses 26 3.6.1 Scanning Electron Microscope (SEM) 26 3.6.2 Energy Dispersive X-ray Spectrometer (EDS) and Mapping 27 3.6.3 X-ray Diffractometer (XRD) 28 3.7 Principles and Procedure of in vitro Studies 29 3.7.1 Cell Viability, Water Soluble Tetrazolium Salts (WST-1) Assay 29 3.7.2 Cytotoxicity, Lactate Dehydrogenase (LDH) Assay 31 3.7.3 Live and Dead Cell Assay 32 3.7.4 Alkaline Phosphatase (ALP) Assay 33 3.8 Principles and Procedure of in vivo Studies 35 3.8.1 Bone Mineral Density (BMD) Test 35 3.8.2 Inorganic Matrix Assessment 36 3.8.3 Serum Biochemistry 36 3.8.4 Histology 37 Chapter Ⅳ Results and Discussion 38 4.1 Materials Characteristic Analyses 38 4.1.1 Morphology of Brushite 38 4.1.2 Elemental Analysis of Brushite 39 4.1.3 Crystal Structure of Brushite 41 4.1.4 Morphology of ANB 42 4.1.5 Elemental Mapping of ANB 44 4.1.6 Calcium Solubility 45 4.2 In vitro Studies 46 4.2.1 Cell Proliferation and Viability, WST-1 Assay 46 4.2.2 Cytotoxicity, Lactate Dehydrogenase (LDH) Assay 47 4.2.3 Live and Dead Cell Assay 48 4.2.4 ALP Assay 49 4.3 In vivo Studies 50 4.3.1 BMD Analysis 50 4.3.2 Inorganic Matrix Assessment 51 4.3.3 Serum Biochemistry 52 4.3.4 Histological Examination 53 Chapter Ⅴ Conclusion 55 References 56 | |
dc.language.iso | en | |
dc.title | 褐藻膠包覆柚皮苷與透鈣磷石作為骨質疏鬆症治療之研究 | zh_TW |
dc.title | The Study of Naringin and Brushite Encapsulated in Alginate Sphere for Osteoporosis | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 郭士民(Shyh-Ming Kuo),曾靖孋(Ching-Li Tseng) | |
dc.subject.keyword | 骨質疏鬆症,透鈣磷石,柚皮苷,骨碎補,褐藻膠, | zh_TW |
dc.subject.keyword | Osteoporosis,Brushite,Naringin,Gu-Sui-Bu,Alginate hydrogel, | en |
dc.relation.page | 62 | |
dc.identifier.doi | 10.6342/NTU202002361 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-05 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 材料科學與工程學研究所 | zh_TW |
顯示於系所單位: | 材料科學與工程學系 |
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