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研究生:林士閎
研究生(外文):LIN, SHIH HUNG
論文名稱:工業化量產製作血小板乾粉
論文名稱(外文):Industrial Mass Production of Platelet Dry Powder
指導教授:方旭偉方旭偉引用關係
指導教授(外文):FANG, HSU-WEI
口試委員:方旭偉王翰聰梁弘人張祐維魏暘莊爾元
口試委員(外文):FANG, HSU-WEIWANG, HAN-TSUNGLIANG, HONG-JENCHANG, YU-WEIWEI, YANGCHUANG ER-YUAN
口試日期:2024-03-25
學位類別:博士
校院名稱:國立臺北科技大學
系所名稱:化學工程與生物科技系博士班
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2024
畢業學年度:112
語文別:中文
論文頁數:79
中文關鍵詞:生長因子富含血小板血漿富含血小板纖維蛋白
外文關鍵詞:growth factorsplatelet-rich plasmaplatelet-rich fibrin
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本論文主要在探討利用豬血進行工業化量產製備血小板乾粉,將血小板乾粉作為一種成本較低且大量生產的原料,因PRP和PRF含有多種生長因子,可被廣泛應用於醫學領域。然而,PRP受限於製備過程的複雜性,PRF受限於製備過程中不添加任何抗凝血劑,大量生產時可能產生凝血現象,PRP和PRF兩者的製作方法皆不適合進行大規模量產,同時自體PRP和自體PRF受限於來源不足也不適合進行大規模量產,這代表產能無法滿足市場需求,製備出多樣化的劑型以適應不同的應用領域。本研究提出了利用豬血製作量產血小板乾粉的方法,豬血不僅取得容易,且豬血來源豐富,供應穩定,成本相對較低,這對於大規模的生產極具吸引力。更重要的是,豬在生物醫學研究中已被廣泛使用,對其生理和血液特性的了解使得我們更容易適應和最佳化其利用。實驗結果表明本研究方法可利用豬血實現大規模的生產血小板乾粉,製備完成的血小板乾粉中含有高濃度生長因子,TGF-β1濃度維持在120,000~140,000 pg/ml的範圍內,而PDGF-BB的濃度則在70,000~90,000 pg/ml之間,血小板乾粉製備12個月後,TGF-β1的濃度相較於製備完成時,TGF-β1的濃度仍保有90%以上,這代表血小板乾粉製程具有高度的可靠性和一致性,可長期保存且品質穩定,不僅能充分利用豬血,減少浪費,還能降低環境負擔,更可以為相關產業提供更多的原料供應,用於後續的產品開發。
This thesis primarily explores the industrial-scale production of platelet powder using porcine blood, positioning platelet powder as a cost-effective and mass-producible raw material. PRP (Platelet-Rich Plasma) and PRF (Platelet-Rich Fibrin) contain multiple growth factors and can be widely applied in medical fields. However, PRP is limited by its complex preparation process, and PRF by the absence of anticoagulants during its preparation, which may lead to coagulation during large-scale production. Therefore, the preparation methods for both PRP and PRF are not suitable for mass production. Additionally, autologous PRP and PRF are constrained by limited sources, making them unsuitable for large-scale production, which means that production capacity cannot meet market demand or produce diverse formulations for various applications.
This study proposes a method for the mass production of platelet powder using porcine blood. Porcine blood is not only easy to obtain but also has abundant and stable sources at a relatively low cost, making it highly attractive for large-scale production. More importantly, pigs have been widely used in biomedical research, and the comprehensive understanding of their physiology and blood characteristics facilitates the adaptation and optimization of their utilization.
The experimental results demonstrate that the method developed in this study can achieve large-scale production of platelet powder using porcine blood. The prepared platelet powder contains high concentrations of growth factors, with TGF-β1 levels maintained between 120,000 and 140,000 pg/ml, and PDGF-BB levels between 70,000 and 90,000 pg/ml. After 12 months of storage, the TGF-β1 concentration in the platelet powder retained more than 90% of its initial level, indicating a high degree of reliability and consistency in the production process. This stability allows for long-term storage and consistent quality, effectively utilizing porcine blood to reduce waste, minimize environmental impact, and provide ample raw material for related industries for further product development.

目錄
摘要 i
ABSTRACT ii
誌謝 iv
表目錄 viii
圖目錄 ix
1 第一章 緒論 1
1.1前言 1
1.2研究動機 3
2 第二章 文獻探討 4
2.1血小板 4
2.1.1血小板顆粒 4
2.2生長因子 7
2.2.1血小板衍生生長因子 8
2.2.2轉化生長因子 8
2.2.3表皮生長因子 9
2.2.4類胰島素生長因子 10
2.2.5肝細胞生長因子 10
2.2.6血管內皮生長因子 11
2.3富含血小板血漿 12
2.3.1富含血小板血漿的應用 12
2.3.2富含血小板血漿的製備 13
2.4富含血小板纖維蛋白 14
2.4.1三維纖維蛋白支架結構 14
2.4.2富含血小板纖維蛋白的應用 15
2.4.3富含血小板的纖維蛋白的製備 16
2.5活化 17
3 第三章 關鍵問題 18
3.1研究目的 18
3.2 PRP與PRF的製備方法 18
3.3自體血液供應不足 19
第四章 實驗方法 21
4.1製作血小板乾粉的方法 21
4.2不同濃度的氯化鈣溶液對血小板濃度的影響 21
4.3不同比例的氯化鈣溶液對血小板濃度的影響 22
4.4不同濃度的氯化鈣溶液對TGF-β、PDGF-BB的影響 22
4.4.1 TGF-β1濃度檢測方法 25
4.4.2 PDGF-BB濃度檢測方法 29
4.5不同比例的氯化鈣溶液對TGF-β1、PDGF-BB的影響 33
4.6不同批次的再現性 33
4.7血小板乾粉保存的檢測 34
4.8 細胞毒性測試 34
4.9皮膚致敏性檢測 38
4.10眼睛刺激性檢測 39
4.11皮膚屏障檢測 41
5 第五章 結果與討論 44
5.1不同濃度的氯化鈣溶液對血小板濃度的影響 44
5.2不同比例的氯化鈣溶液對血小板濃度的影響 44
5.3不同濃度的氯化鈣溶液對TGF-β、PDGF-BB的影響 45
5.4不同比例的氯化鈣溶液對TGF-β1、PDGF-BB的影響 48
5.5不同批次的再現性 49
5.6血小板乾粉保存的檢測 51
5.7 細胞毒性試驗 52
5.8皮膚致敏性檢測 55
5.9眼睛刺激性檢測 56
5.10皮膚屏障檢測 57
6 第六章 討論 58
6.1量產血小板乾粉 58
6.2血小板乾粉具有良好的生物相容性 59
6.3活化劑比較 59
6.4不同物種的血小板乾粉應用 61
6.5凍乾粉的保存期限 62
6.6豬血替代人血 62
7 第七章 結論 64
參考文獻 65
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