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懸壅垂腭咽成形術對於阻塞性睡眠呼吸中止症患者其心血管相關疾病之預防效果

為了解決precipitate中文醫學的問題，作者林以志 這樣論述：

中文摘要1 背景:從過去的研究發現，阻塞型睡眠呼吸中止症的病人似乎有較高的機會得到心血管疾病，其中包括了高血壓、心律不整、新陳代謝症候群、冠狀動脈及腦血管疾病。其潛在的機轉主要有三個，分別是1. 缺氧導致交感神經的活化2. 血管內皮功能障礙 3. 全身系統性的發炎反應。治療阻塞性睡眠呼吸中止症obstructive sleep apnea, OSA的首選是陽壓呼吸器continuous positive airway pressure, CPAP。使用陽壓呼吸器以後，對於阻塞性睡眠呼吸中止症OSA患者罹患高血壓或是頑固性高血壓，都可以降低血壓，且能降低心血管病併發症以及減少因為心血管引起的

死亡。然而，臨床上病人願意持續配戴陽壓呼吸器的比率不高。因此，臨床上考慮替代的治療方案，例如上呼吸道的手術、口腔裝置。而其中懸壅垂顎咽成形術uvulopalatopharyngoplasty, UPPP則是一種最常見的上呼吸道手術。UPPP在臨床上除了可以治療阻塞性睡眠呼吸中止症，同時亦有研究指出UPPP亦可以如同CPAP對於OSA病人一樣，可改善血壓，也可有效地減少鬱血性心臟衰竭和心房顫動的風險。截至目前為止，並沒有太多的文獻對於UPPP在OSA病人上，對於重大心血管事件(包括急性心肌梗塞, 冠狀動脈粥樣硬化、心房顫動、心室顫動、心衰竭、中風)的預防功效做過評估，此外亦沒有探討對於OSA病人

的慢性病是否有影響，如高血壓、糖尿病、心血管疾病(非重大心血管事件)、高血脂、慢性腎臟病疾病。2 研究目的以及材料方法：本研究為回溯性世代研究，回溯雙和醫院2009-2016的病歷資料，主要對象為阻塞性睡眠呼吸中止症OSA的病人，且有在雙和醫院接受多項睡眠生理檢查polysomnography, PSG者，研究者擬使用電子病歷追蹤到2020年，想要知道懸壅垂顎咽成形術對於阻塞性睡眠呼吸中止症的影響，分為3個子研究。2.1 第一個子研究:評估手術對於重大心血管事件(包括急性心肌梗塞, 冠狀動脈粥樣硬化、心房顫動、心室顫動、心衰竭、中風)，是否具有預防效果。選取三組做比較，分別是UPPP、CP

AP、以及未接受任何睡眠呼吸中止症相關治療的對照組，來評估UPPP相對於其他兩組，是否有所差異。2.2 第二個子研究:評估手術對於高血壓，是否有預防效果。選取三組做比較，分別是UPPP、CPAP、以及未接受任何睡眠呼吸中止症相關治療的對照組，來評估相對於對照組，是否有所差異。2.3 第三個子研究:評估手術對於阻塞性睡眠呼吸中止症相關的心血管共病症，如糖尿病、心血管疾病(非重大心血管事件)、高血脂、慢性腎臟病疾病，是否有預防效果。選取三組做比較，分別是UPPP、CPAP、以及未接受任何睡眠呼吸中止症相關治療的對照組，來評估相對於對照組，是否有所差異。3 預期結果：3.1 第一子研究:

懸壅垂顎咽成形術相比於對照組，對於重大心臟不良事件有較好的預防效果。 懸壅垂顎咽成形術相對於陽壓呼吸器，則是具有相似的保護效果。3.2 第二子研究: 懸壅垂顎咽成形術相比於對照組，對於高血壓有較好的預防效果。 懸壅垂顎咽成形術相對於陽壓呼吸器，則是具有相似的保護效果。3.3 第三子研究: 懸壅垂顎咽成形術相比於對照組，在心血管相關的慢性病，如糖尿病、慢性腎臟病、心血管疾病、高血脂症具有較好的保護效果。

新型溫感性凝膠負載雙特異性T細胞接合抗體於原位皮下注射之研發與臨床應用

為了解決precipitate中文醫學的問題，作者魏溥陞 這樣論述：

目錄致謝 I中文摘要 IIAbstract III目錄 V圖目錄 X表目錄 XVIII第一章 緒論 20一、 單株抗體 211. 單株抗體之結構特性 212. 單株抗體之製備方式 213. 單株抗體之作用原理與種類 22二、 雙特異性抗體 251. 基礎結構與治療策略 252. 臨床發展所面臨之困境 283. Blinatumomab 31三、 蛋白質之控釋策略 321. 聚乙二醇化系統 342. 反溶劑遞送系統 353. 水膠體遞送系統 36第二章 實驗動機與目的 42第三章 實驗試劑與儀器 44一、 藥品與材料

44二、 細胞實驗材料 47三、 儀器 48第四章 實驗方法 50一、 二嵌段共聚物 (DP) 和三嵌段共聚物 (TP) 的合成 521. 二嵌段共聚物之合成 522. 三嵌段共聚物之合成 523. 核磁共振光譜分析 554. 膠體滲透層析分析 55二、 複合水凝膠 (DTgel) 的製備 571. DTgel的設計、配置與篩選 572. DTgel的成膠溫度與收縮量 583. DTgel的溶液-凝膠轉變溫度的測定 594. DTgel的流變特性 59三、 負載BiTEE之複合水凝膠 (BiTEE/DTgel) 的製備 601. BiTEE

凍晶乾燥粉末的製備與安定性試驗 602. BiTEE/DTgel的製備與安定性試驗 603. BiTEE/DTgel的含量分析 614. BiTEE/DTgel的流變特性 62四、 BiTEE/DTgel的體外釋放性質與模式分析 631. BiTEE/DTgel的體外釋放曲線 632. BiTEE/DTgel的體外釋放模式評估 63五、 BiTEE/DTgel的體內藥物動力學評估 651. 血漿檢品之BiTEE含量分析 652. BiTEE/DTgel與BiTEE溶液的體內藥物動力學評估 663. 不同劑量之BiTEE/DTgel體內藥物動力學評估 6

6六、 BiTEE/DTgel對人源系T細胞小鼠的體內毒性研究 671. 人源系T細胞 (TALL-104) 之培養 672. 人源系T細胞小鼠的模式建立 673. BiTEE/DTgel於人源系T細胞小鼠之體內毒性研究 67七、 BiTEE/DTgel在MDA-MB-231異種移植之人源系T細胞小鼠模型中的抗腫瘤功效 691. MDA-MB-231異種移植之人源系T細胞小鼠模型建立 692. BiTEE/DTgel在MDA-MB-231異種移植之人源系T細胞小鼠模型之T細胞活體成像與腫瘤治療功效分析 713. BiTEE/DTgel於實體腫瘤組織中的T細胞募集與

組織安全性分析 71八、 不同劑量之BiTEE/DTgel在MDA-MB-231異種移植之a-huPBMCs小鼠模型中的T細胞活體成像與腫瘤治療功效分析 721. 人類PBMC (huPBMCs) 之分離、活化與染色 722. MDA-MB-231異種移植之a-huPBMCs小鼠模型建立 723. MDA-MB-231異種移植之a-huPBMCs小鼠模型之T細胞活體成像與腫瘤治療功效分析 73九、 統計分析 74第五章 實驗結果與討論 75一、 二嵌段共聚物 (DP) 和三嵌段共聚物 (TP) 的製備與特性檢測 75二、 DTgel的性質分析與流變學分析 80

1. DTgel的設計與性質分析 802. DTgel的水滲出比例特性 843. DTgel的溶液－凝膠相變圖 (Sol-gel transition phase diagram) 854. DTgel的流變特性 86三、 負載BiTEE之複合水凝膠 (BiTEE/DTgel) 的製備 881. BiTEE的分析確效 882. BiTEE凍乾粉末的安定性分析 903. BiTEE/DTgel的含量分析 914. BiTEE/DTgel的安定性分析 915. BiTEE/DTgel的流變分析 93四、 BiTEE/DTgel的體外釋放性質與模式分析 9

51. BiTEE/DTgel的體外釋放試驗 952. BiTEE/DTgel的體外釋放模式評估 96五、 BiTEE/DTgel的體內藥物動力學評估 981. 血漿中BiTEE的分析確效 982. BiTEE/DTgel與無膠體負載BiTEE的體內藥物動力學評估 1003. 不同劑量之BiTEE/DTgel體內藥物動力學評估 104六、 BiTEE/DTgel對T細胞小鼠的體內毒性研究 107七、 BiTEE/DTgel在MDA-MB-231異種移植之人源系T細胞小鼠模型中的抗腫瘤功效 1111. BiTEE/DTgel在MDA-MB-231異種移植之T細胞

小鼠模型中的抗腫瘤功效 (小腫瘤模型) 1112. BiTEE/DTgel在MDA-MB-231異種移植之T細胞小鼠模型中的抗腫瘤功效 (大腫瘤模型) 1143. BiTEE/DTgel於實體腫瘤組織中的T細胞募集與組織安全性分析….. 120八、 不同劑量之BiTEE/DTgel在MDA-MB-231異種移植a-huPBMCs小鼠模型中的T細胞活體追蹤成像與腫瘤治療功效分析 1251. BiTEE/DTgel在MDA-MB-231異種移植之a-huPBMCs小鼠模型中的T細胞活體追蹤成像 (大腫瘤模型) 1252. BiTEE/DTgel在MDA-MB-231異種移植之a

-huPBMCs小鼠模型中的腫瘤療效分析 (大腫瘤模型) 131第六章　結論 134第七章　參考文獻 135圖目錄Figure 1-1. Timeline from 1975 showing the successful development of therapeutic antibodies and their applications [1]. 20Figure 1-2. Mechanisms of action of therapeutic antibodies [5]. 22Figure 1-3. IgG and various fragments thereof toge

ther with detail of the antigen binding Fab region [8]. 24Figure 1-4. Schematic overview of the proposed mechanisms of action for bispecific antibodies (bsAbs) in clinical trials for oncology. 1. Engagement of immune cells to the tumor cell. Immune cells can be engaged to tumor cells. 2. Targeted d

elivery of payloads. Tumor cells are being targeted with a bsAb having affinity for both the tumor and a payload. 3. Blocking signaling. Two targets are being disrupted by the bsAb [13]. 26Figure 1-5. (a) Normal major histocompatibility complex (MHC)-dependent targeting of tumour antigens by T cell

s via the T cell receptor (TCR). (b) MHC-independent targeting of tumour-associated antigens (TAAs) via the use of a bispecific T cell engager (BiTE) to activate T cells by linking the TAA to CD3ε of the TCR complex; a transient BiTE-induced cytolytic synapse enables perforin and granzyme-mediated d

estruction of the targeted tumour cell via activation of the proteolytic caspase signalling pathway [14]. 27Figure 1-6. Schematic overview of the proposed mechanisms of action for bispecific antibodies (bsAbs) in clinical trials for oncology [13]. 29Figure 1-7. Pathophysiology of cytokine release

syndrome [16]. 29Figure 1-8. (a) Serum peak cytokine concentrations after initiation of blinatumomab, (b) cytokine concentrations over time in an individual patient after initiation of Blinatumomab [19]. 31Figure 1-9. Relative frequency distribution of protein drugs by protein function [20]. 32Fi

gure 1-10. Processes involved in SC absorption [23]. 34Figure 1-11. Schematic representation of in situ forming (ISF) PLGA drug delivery implants formation, solvent exchange and drug release [28]. 35Figure 1-12. Dorsal view from an unrestrained, conscious wild-type mouse, captured by IR thermograp

hy (T335, FLIR Systems), demonstrating heterogeneity in surface temperatures by color coding. The ambient temperature was set to 22–23°C [37]. 37Figure 1-13. The degradation behavior of mPEG-PLGA diblock copolymer determined by the weight lost method [48]. 40Figure 1-14. Characterization of the th

ermosensitive hydrogel. (a) Storage modulus (G’) of the blank PLGA-PEG-PLGA hydrogel. (b) Release profiles of protein from the hydrogel. Inset is the release profile of the first 12 hours [50]. 41Figure 4-1. Synthetic schematic of diblock copolymer and triblock copolymer used mPEG or PEG as the ini

tiator. 54Figure 4-2. Schematic diagram of BiTEE detected by enzyme-linked immunosorbent assay (ELISA) used anti-human Fab and anti- histidine tag 62Figure 4-3. Experimental protocol of in vivo toxicity study of BiTEE/DTgel in TALL-104 cells injected SCID mice 68Figure 4-4. Experimental protocol

of in vivo anti-tumor study of BiTEE/DTgel in TALL-104 cells injected MDA-MB-231 bearing SCID mice 70Figure 4-5. Experimental protocol of in vivo anti-tumor study of BiTEE/DTgel-2S with different dosage of BiTEE in a-huPBMCs injected MDA-MB-231 bearing SCID mice 73Figure 5-1. The 1H NMR spectrum o

f mPEG-PLGA diblock copolymer (DP) and PLGA-PEG-PLGA triblock copolymer (TP) 77Figure 5-2 Calibration curve of polystyrene standard in chloroform 79Figure 5-3 The GPC curves of mPEG-PLGA diblock copolymer (DP) and PLGA-PEG-PLGA triblock copolymer (TP) 79Figure 5-4. (A) Schematic illustration of D

Tgel and DPgel with differet structure stability at 37 ℃ (B) The images of DTgel-C and DPgel-1 at 4 ℃, 25 ℃ and 37 ℃ 82Figure 5-5. Shrinkage studies of DTgel-1, DTgel-2, DTgel-2S and DPgel-1 at 37 ℃. 84Figure 5-6. Sol-gel transition phase diagram of DTgel-1, DTgel-2, DTgel-2S and DPgel-1 85Figure

5-7. Rheological characteristics of DTgel-1, DTgel-2 and DTgel-2S in dynamic temperature ramp test 87Figure 5-8. Interday calibration curve of BiTEE in solution. 89Figure 5-9. Stability studies of BiTEE lyophilized powder with different stabilized agent at 4 ℃. Data are expressed as mean ± SD (n

= 3). 90Figure 5-10. The Stability of BiTEE in BiTEE/DTgels at 4 ℃. Data are expressed as mean ± SD (n = 3). 92Figure 5-11. The Stability of BiTEE in BiTEE/DTgels at 25 ℃. Data are expressed as mean ± SD (n = 3). 92Figure 5-12. Rheological characteristics of BiTEE/DTgel-1, BiTEE/DTgel-2 and BiTEE

/DTgel-2S in dynamic temperature ramp test 94Figure 5-13. In vitro release profile of BiTEE/DTgel-1, BiTEE/DTgel-2, BiTEE/DTgel-2S and BiTEE/DPgel-1. Data are expressed as mean ± SD (n = 3). 96Figure 5-14. Interday calibration curve of BiTEE in plasma. 99Figure 5-15. In vivo pharmacokinetic profi

les of i.v. BiTEE solution through a tail vein, s.c. BiTEE solution, BiTEE/DTgel-1, BiTEE/DTgel-2 and BiTEE/DTgel-2S (5 mg/kg) in male BALB/c mice. Data are expressed as mean ± SD (n = 3) 102Figure 5-16. In vivo pharmacokinetic profiles of BiTEE/DTgel-2S with different BiTEE doses (mg/kg) in male B

ALB/c mice. Data are expressed as mean ± SD (n = 5). 105Figure 5-17. Linear regression between AUC0-inf and BiTEE doses in BiTEE/DTgel-2S 106Figure 5-18. Linear regression between Cmax and BiTEE doses in BiTEE/DTgel-2S 106Figure 5-19. The change of rectal temperature in SCID mice injected with T

cells after being administered an i.v. BiTEE solution (at 5 mg/kg body weight), and s.c. BiTEE solution, BiTEE/DTgel-1, BiTEE/DTgel-2, and BiTEE/DTgel-2S (at 5 or 10 mg/kg body weight) (n=3) 109Figure 5-20. The release of IFN-γ in SCID mice injected with T cells after being administered an i.v. BiT

EE solution (at 5 mg/kg body weight), and s.c. BiTEE solution, BiTEE/DTgel-1, BiTEE/DTgel-2, and BiTEE/DTgel-2S (at 5 or 10 mg/kg body weight) (n=3) 109Figure 5-21. The release of TNF-α in SCID mice injected with T cells after being administered an i.v. BiTEE solution (at 5 mg/kg body weight), and

s.c. BiTEE solution, BiTEE/DTgel-1, BiTEE/DTgel-2, and BiTEE/DTgel-2S (at 5 or 10 mg/kg body weight) (n=3) 110Figure 5-22. The release of IL-2 in SCID mice injected with T cells after being administered an i.v. BiTEE solution (at 5 mg/kg body weight), and s.c. BiTEE solution, BiTEE/DTgel-1, BiTEE/D

Tgel-2, and BiTEE/DTgel-2S (at 5 or 10 mg/kg body weight) (n=3) 110Figure 5-23. In vivo efficacy of BiTEE/DTgel-1, BiTEE/DTgel -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =75 mm3). Data are expressed as mean ± SD (n = 3~5).

112Figure 5-24. Body weight change of BiTEE/DTgel-1, BiTEE/DTgel-2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =75 mm3). Data are expressed as mean ± SD (n = 3~5). 113Figure 5-25. In vivo efficacy of BiTEE/DTgel-1, BiTEE/DTg

el -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). Data are expressed as mean ± SD (n = 4~5). 115Figure 5-26. Body weight change of BiTEE/DTgel-1, BiTEE/DTgel -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE s

olution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). Data are expressed as mean ± SD (n = 4~5). 115Figure 5-27. In vivo images of mice injected with MDA-MB-231 xenograft DiR-labeled TALL-104 cells after being administrated the intravenous (i.v.) BiTEE solution, and subcutaneous

(s.c.) BiTEE solution, BiTEE/DTgel-1, BiTEE/DTgel-2, and BiTEE/DTgel-2S (5 mg/kg body weight) at 3, 24, 52, and 72 h with an IVIS spectrum optical imaging system. 117Figure 5-28. The total radiant efficiency of tumor site in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3) at 3, 24, 52 and 72  

hr with an IVIS spectrum optical imaging system after being administration with BiTEE/DTgel-1, BiTEE/DTgel -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg). Data are expressed as mean ± SD (n = 3). 118Figure 5-29. The total radiant efficiency of liver in MDA-MB-231 tumor-b

earing mice (tumor size =150 mm3) at 3, 24, 52 and 72 hr with an IVIS spectrum optical imaging system after being administration with BiTEE/DTgel-1, BiTEE/DTgel -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg). Data are expressed as mean ± SD (n = 3). 118Figure 5-30. The t

otal radiant efficiency of injection site in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3) at 3, 24, 52 and 72  hr with an IVIS spectrum optical imaging system after being administration with BiTEE/DTgel-1, BiTEE/DTgel -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg).

Data are expressed as mean ± SD (n = 3). 119Figure 5-31. Immunohistochemical staining (CD8) images of BiTEE/DTgel-1, BiTEE/DTgel -2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). 122Figure 5-32. The quantization of C

D8+ signals in IHC images using ImageJ 123Figure 5-33. IHC staining images of granzyme B in MDA-MB-231 tumors (150 mm3 in tumor volume) on day 21 after administration. Scale bar = 200 µm. 123Figure 5-34. Histologic analysis of kidney, spleen and liver after injection of BiTEE/DTgel-1, BiTEE/DTgel

-2, BiTEE/DTgel -2S, s.c. BiTEE solution and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). 124Figure 5-35. Mice imaged at 2, 6, 12, 24, 52, 72, and 96 hr with an IVIS spectrum optical imaging system after being administered with BiTEE/DTgel-2S loaded the dosa

ge of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg) 127Figure 5-36. The total radiant efficiency of tumor site at 2, 6, 12, 24, 52, 72, and 96 hr with an IVIS spectrum optical imaging system after being administration with BiTEE/DTgel-2S lo

aded the dosage of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg). Data are expressed as mean ± SD (n = 3). 128Figure 5-37. The total radiant efficiency of liver at 2, 6, 12, 24, 52, 72, and 96 hr with an IVIS spectrum optical imaging system

after being administration with BiTEE/DTgel-2S loaded the dosage of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg). Data are expressed as mean ± SD (n = 3). 129Figure 5-38. The total radiant efficiency of injection site at 2, 6, 12, 24, 52,

72, and 96 hr with an IVIS spectrum optical imaging system after being administration with BiTEE/DTgel-2S loaded the dosage of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg). Data are expressed as mean ± SD (n = 3). 130Figure 5-39. In vivo

efficacy of BiTEE/DTgel-2S loaded the dosage of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). Data are expressed as mean ± SD (n = 3~5). 132Figure 5-40. Body weight change of BiTEE/DTg

el-2S loaded the dosage of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). Data are expressed as mean ± SD (n = 3~5). 132Figure 5-41. The tumor images after the treatment of BiTEE/DTgel-

2S loaded the dosage of 5 mg/kg, 2.5 mg/kg, 1 mg/kg, 0.25 mg/kg, s.c. BiTEE solution (5 mg/kg) and i.v. BiTEE solution (5 mg/kg) in MDA-MB-231 tumor-bearing mice (tumor size =150 mm3). 133表目錄Table 1-1 Tumor-associated antigens targeted by therapeutic monoclonal antibodies in oncology [4]. 23Table

1-2 Clinical trials of BiTE in recent years [13]. 30Table 1-3 Research findings on antisolvent delivery system of biologics [29]. 36Table 1-4. List of biotherapeutic molecules delivered by PEG-PLGA thermosensitive hydrogels [49, 50, 53, 55]. 40Table 4-1. Abbreviations and full names of the materi

als and formulations in this study. 50Table 4-2. Formula for each diblock copolymer and triblock copolymer 53Table 4-3. Different formulation of 15% DTgel prepared with high and low PLGA/PEG ratio copolymer in the ratio of 1:1 57Table 4-4. Formula of modified 15% DTgel by adjustment of copolymer

ratio and total salt content and unmodified 15% DPgel 58Table 4-5. Formula of stabilized BiTEE powder 60Table 5-1. Integral H1NMR signals and physical properties of mPEG-PLGA diblock copolymer (DP) and PLGA-PEG-PLGA triblock copolymer (TP) 78Table 5-2. Effect of different single and composite hyd

rogels 82Table 5-3. The gelling temperature and gel strength of DPgel-1 and DTgel by adjustment of copolymer ratio and total salt content 83Table 5-4. Interday precision and accuracy of BiTEE in solution. 89Table 5-5. The BiTEE content in BiTEE/DTgel-1, BiTEE/DTgel-2 and BiTEE/DTgel-2S 91Table 5

-6. The cumulative release and release kinetic model of BiTEE/DTgel-1, BiTEE/DTgel-2, BiTEE/DTgel-2S and BiTEE/DPgel-1 (n=3). 97Table 5-7. Interday precision and accuracy of BiTEE in plasma. 99Table 5-8. Pharmacokinetic parameters of i.v. BiTEE solution through a tail vein, s.c. BiTEE solution, Bi

TEE/DTgel-1, BiTEE/DTgel-2 and BiTEE/DTgel-2S (5 mg/kg) in male BALB/c mice. Data are expressed as mean ± SD (n = 3) 103Table 5-9. Pharmacokinetic parameters of BiTEE/DTgel-2S with different BiTEE doses (mg/kg) in male BALB/c mice. Data are expressed as mean ± SD (n = 5). 105