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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林?輝(Feng-Huei Lin) | |
dc.contributor.author | HU MENG | en |
dc.contributor.author | 孟虎 | zh_TW |
dc.date.accessioned | 2021-06-08T02:12:21Z | - |
dc.date.copyright | 2016-02-24 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-01-18 | |
dc.identifier.citation | Rachner, T. D., Khosla, S., Hofbauer, L.C.(2011). Osteoporosis: now and the future. The Lancet, 377(9773), 1276-1287.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19667 | - |
dc.description.abstract | 目前,世界上年齡超過五十歲時,由於低骨密度有三分之一的女人和五分之一的男人都會遭受骨折。有百分之三十三的老年人,當他們發生胯關節骨折的時候會喪失一定的自我勞動能力,因此導致喪失獨立的生活能力。但是因為此而導致更不幸的是,在在骨折隨後的一年內所導致的死亡率達到了五分之一。
當前的預防藥物不僅僅需要支付高昂的醫藥費用,而且目前的預防藥物藥物還有很多的副作用,這些副作用有些事因為一次使用大劑量的藥物量所導致,然而當小劑量使用藥物時候,儘管副作用有所減小,但是病人的依從性卻非常差。目前使用的抗骨質疏鬆的藥物中,除了其花費昂貴等缺點,還有一些其他諸多的弊病,如:由於藥物設計的不夠巧妙,導致使用時藥物的劑量過高或過低而導致病人發生很嚴重的副作用或使用過程中出現很差的依從性。因此為瞭解決這些問題。我們嘗試一種新的中藥成份柚皮苷與鍶摻雜的氫氧基磷灰石相結合的方式來提高預防骨質疏鬆的效果。 我們希望藥物有促進成骨細胞增生與分化的作用,柚皮苷是中藥Gu-Sui-Bu中最有效的成分,在正常劑量下,其副作用很低。 柚皮苷是中藥Gu-Sui-Bu中最有效的成分,在正常使用的劑量下,他沒有副作用,同時,它的一個有效的作用就是促進成骨細胞的增生和分化。 氫氧基磷灰石相比較其他目前使用在預防骨質疏鬆的材料,相比較與聚合物,他的降解的時間更長,氫氧基磷灰石同時也是骨的化學組成成分,相對於其他材料來說,這種材料有更低的毒性並且容易製備。 當氫氧基磷灰石中的鈣離子被Sr離子取代時,這時可以增加成骨作用同時降低骨質的吸收,不僅如此,根據前人報導,由於Sr離子的加入,他還展示出了更好的生物相容性。 氫氧基磷灰石,它是骨骼的主要組成成分,他容易製備,並且無毒性,相比其他目前所使用的藥物載體,氫氧基磷灰石降解速率緩慢,同時在酸性的環境下,可以如其他載體一樣降解。當鈣離子部分的被鍶離子所取代的時候,鍶摻雜的氫氧基磷灰石可以增加成骨作用的同時抑制骨被吸收。 柚皮苷可以增強骨保護素的相關基因表達,同時增加了骨保護素與破骨細胞分化因數的比值以達到抑制破骨細胞的活性,降低骨被吸收的過程。骨組織的形成同時還顯著的受到骨鈣素(Osteocalcin, OCN),鹼性磷酸酶的活性的調控,如此一個相對高的骨形成過程,成功的取代骨組織流失的部位。由此一個隨著時間的流逝,骨組織的淨增長會增強骨組織的力學等性質,由此減少骨質疏鬆,減少骨折的發生。 我製作了一個經肌肉注射的新劑型,從藥物載體的設計,到測試該種新劑型可以有增加骨組織,減少骨組織被吸收的雙重的作用,從而達到預防骨質疏鬆的目的。 | zh_TW |
dc.description.abstract | Around the world, at least 1 in 3 women and 1 in 5 men over the age of 50 will suffer a fracture caused by weak bones. Thirty-three percent of older adults who suffer a hip fracture become physically impaired and lose their ability to live independently one year after the fracture. But the most unfortunate is “At least one in five will die within the year following fracture”.
At present, except the high cost of the preventive medications, which also have many side effects, some of the serious side effects are caused by large dose once used. And also the patients don’t have a good compliance with lower-side-effects medications. Besides the high cost of commercial anti-osteoporotic medications, there are still many shortages including serious side effects caused by overdose and poor compliances caused by poor designs of drug administrations. To solve these two problems, we tried to synthesize a novel compound, strontium-dopped hydroxyapatite combined with naringin, to improve the results of Osteoporosis prevention. One of the pharmacological effects is to promote differentiation and proliferation of osteoblast. Naringin is the most effective active ingredient in this medication. Low side effect medications, we chose the active ingredient of Gu-Sui-Bu, a Chinese medication, which doesn’t have side effects when using in low dose. Naringin is the most active ingredient of Gu-Sui-Bu, a Chinese herb medicine with no side effects in regular dosage, and one of naringin’s pharmacological effects is to promote the differentiation and proliferation of osteoblasts. Hap in Comparison with the most other materials currently used in preventative carriers is better, as most of the Polymers degrade faster and don’t have long term effects. Hap is a composition of bone, the advantages in comparison with other materials is that it has low toxicity and it’s easy to prepare. When the calcium partially substituted by Strontium, which can increase Osteogenesis and decrease the bone resorption and it also shows a good biocompatibility as previous study. Hydroxyapatite (Hap), the major composition of bone, is easy to prepare and not toxic. Compared with other materials currently used as a drug carrier, hydroxyapatite degrades slowly and does not acidify surrounding tissues after rapid degradation as polymer carriers do. When the calcium irons inside the molecular structure of hydroxyapatite are partially replaced by strontium irons, this strontium doped hydroxyapatite (Sr-Hap) can increase osteogenesis and decrease the bone resorption with good biocompatibilities. The Naringin can normally stimulate OPG (Osteoprotegerin) expression tipping the OPG/RANKL(Receptor activator of nuclear factor kappa-B ligand,RANKL) ratio in favor of RANKL-inhibited osteoclast activity and decelerate bone resorption. And bone formation is also increased by OCN (Osteocalcin), ALP (Alkaline phosphatase) significantly, it does so at a relatively higher rate where the bone forming capacity of osteoblasts successfully totally replace the lost bone. Thus, a net growth of bone occurs over time that can be associated with decreased fracture risk. We developed a new intramuscular dosage form, from drug carrier design to a new intramuscular dosage form which have dual-effects ‘Atiresorptive’ and ‘Anabolic’ for prevention of Osteoporosis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:12:21Z (GMT). No. of bitstreams: 1 ntu-105-R03548058-1.pdf: 4872507 bytes, checksum: 8a0b57ad737e9c5e68666c53d42d90d0 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 目錄
目錄 1 致謝 3 圖目錄 5 表目錄 6 中文摘要 7 Abstract 9 第一章 序言 11 1.1 骨質疏鬆概況 11 1.2 當前骨質疏鬆症治療策略 13 1.3 骨碎補及其藥理作用 15 1.3.1 骨碎補的補肝腎強筋骨作用 16 1.3.2 骨碎補的抗炎作用 18 1.3.3 骨碎補對牙齒生長及骨質疏鬆的作用 18 1.3.4 預防鏈黴素(Streptomycin)和卡拉黴素(Kalamycin)發生的不良反應 21 1.3.5 降血脂作用 21 1.3.6 其他藥理作用 22 1.4 研究目的 24 第二章 理論基礎 25 2.1 氫氧基磷灰石 25 2.2 鍶離子取代部分鈣離子的Hap及其作用 25 第三章 實驗方法 29 3.1 實驗流程 29 3.2 實驗儀器 30 3.3 實驗藥品 31 3.4 鍶部分取代Hap及Hap藥物載體的合成 32 3.5 載有Naringin氫氧基磷灰石材料的合成 34 3.6 細胞培養 34 3.7 材料分析原理 35 3.7.1 X-ray繞射儀晶體分析 35 3.7.2 傅裡葉轉換紅外線光譜(FT-IR Spectrometer) 36 3.7.3 熱失重分析儀(Thermal Gravity Analysis TGA) 37 3.7.4 粒徑/表面電荷分析儀 38 3.7.5 場發射掃描式電子顯微鏡(SEM) 40 3.7.6 能量散佈光譜儀(EDX) 40 3.7.7 透射電子顯微(Transmission Electron Microscopy, TEM) 41 3.7.8 乳酸脫氫酶(lactate dehydrogenase, LDH)細胞毒性測試 42 3.7.9 WST-1細胞增殖及其細胞毒性測試 43 3.7.10 骨形成蛋白相關基因表達 44 第四章 結果與討論 46 4.1 材料合成與表徵 46 4.1.1 X-ray繞射儀晶體分析 46 4.1.2 傅裡葉轉換紅外線光譜(FT-IR Spectrometer) 47 4.1.3 熱失重分析儀(Thermal Gravity Analysis, TGA) 48 4.1.4 粒徑/表面電荷分析儀 49 4.1.5 場發射掃描式電子顯微鏡及能量散佈光譜儀 50 4.1.6 透射電子顯微鏡 51 4.1.7 材料的溶液穩定性分析 54 4.1.8 成核機理與Naringin嵌入方式 55 4.1.9 LDH細胞毒性測試 56 4.1.10 WST-1細胞增生毒性測試 57 4.1.11 骨形成蛋白相關基因表達 58 4.1.12 新劑型藥物作用方式 59 第五章 結論 60 參考文獻 61 | |
dc.language.iso | zh-TW | |
dc.title | 骨質疏鬆預防新策略:鍶摻雜的氫氧基磷灰石與藥物柚皮苷之結合的製備,表徵與體外評估 | zh_TW |
dc.title | Strontium-dopped hydroxyapatite combined with Naringin as a new strategy for Osteoporosis prevention: Preparation, Characterization and In-Vitro Evaluation | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳克紹(Ke-Shao Chen),張國基(Guo-Ji Zhang),黃義侑(Yi-You Huang),吳長晉(Chang-Jin Wu),楊禎明(Zhen-Ming Yang) | |
dc.subject.keyword | 骨質疏鬆症,鍶元素,柚皮?,氫氧基磷灰石, | zh_TW |
dc.subject.keyword | Osteoporosis,Strontium,Naringin,Hydroxyapatite, | en |
dc.relation.page | 66 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2016-01-19 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
顯示於系所單位: | 醫學工程學研究所 |
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