臺灣博碩士論文加值系統

本研究開發出一種具有生物親和性、光反硬性及快速成膜性的新型感光明膠。在醇水的介質中，利用dicyclohexyl- carbodiimide (簡稱DCC)作為在醯胺反應(amide formation)中羧酸基和胺基之結合劑。明膠和glycine是反應中胺基的供應來源。當每一個3,3',4,4'-benzophenone tetra-carboxylic di-anhydride (BTDA) 分子的雙酐基與導入的2-hydroxyethyl methacrylate (HEMA)分子進行開環反應(ring-opening reaction)，BTDA將開環產生四個羧酸基，其中兩個與HEMA進行加成反應結合而生成感光性的明膠，稱之為GE-BTHE。 其中BTDA分子中的ketone基成為光反應的主要元件而HEMA本身的雙鍵則成為交聯所必需的雙鍵提供者。這樣的組合使得光反應性的明膠可以藉由高壓水銀燈(high pressure mercury lamp)經六分鐘的照射之後，由原本透明的溶液轉變為膨潤的不透光薄膜。經實驗分析發現，最有效的照射波長為267 nm而成膜的GE-BTHE最高所能達到的膨潤度為5.9。機械性質部份，乾膜仍然可保有延展度達5-10%，這表示GE-BTHE的乾膜也具有些許的彈性。 GE-BTHE合成還經由醯胺反應的分析來計算其膠聯度、膨潤比並監測其光反應的過程。 GE-BTHE膜也利用atomic force microscopy (AFM), scanning electron microscopy (SEM) 和UV-vis spectroscopy等儀器來進行表面、切面及結構的分析。 藉由這些分析，可以得知UV的照射反應使得GE-BTHE膜同時產生了光交聯反應及光裂解的反應。光交聯反應其最大的吸收波長介於267~275 nm之間，表示在此波長範圍交聯程度遠大於裂解程度。而在254 nm波長照射下發生了所謂相轉移的情形，表示裂解程度大於交聯程度。本研究的許多結果相當具有潛力利用於工業或醫學方面的應用。且藉由控制光膠聯與光裂解，更能使GE-BTHE膜應用的更為廣泛，例如:傷口的保護、止血材料的製造更可推廣至先進的微影手術或血管支架等。

A novel bio-affinitive, photocuring and membrane-forming gelatin derivative was synthesized in this study. This process was based on the amide formation between carboxylic acid and the amine in methanol-water media using dicyclohexyl- carbodiimide (DCC) as a condenser. Gelatin and glycine were the sources of amine in the model reaction. Since there were two anhydride groups in each 3,3',4,4'-benzophenone tetra-carboxylic di-anhydride (BTDA) molecule, two 2-hydroxyethyl methacrylate (HEMA) molecules were used to induce the ring-opening reaction of BTDA and release two carboxylic acid groups. The resulting photoreactive gelatin was called GE-BTHE, of which the photoreactive component was the ketone groups of BTDA and HEMA that played the role of double bond supplier. This photoreactive gelatin could be converted from the transparent liquid phase into swollen membrane by a 6-minute irradiation of high pressure mercury lamp. The most efficient irradiation was at 267 nm and the highest degree of swelling of the cured GE-BTHE membrane could reach 5.9. The elongation from the dried gel remained 5-10%, i.e. relatively elastic. The properties of this gelatin derivative were investigated using amide formation analysis, calculation of the gel content and the swelling ratio, and monitoring of the photocuring process. The membranes of GE-BTHE were also examined with atomic force microscopy (AFM), scanning electron microscopy (SEM) and UV-vis spectroscopy. The results revealed that UV irradiation could bring about both photo-crosslinking as well as photo-degradation in the GE-BTHE membrane. The maximum absorbance of UV irradiation occurred in the range of 267 to 275 nm. Once the membrane was further irradiated at 254 nm, phase transformation took place. The GE-BTHE synthesized in this study should be very potential in biomedical and industrial applications. Furthermore, the photo-crosslinking and photo- degradation behavior of GE-BTHE also makes it more useful such as protective wound dressings and hemostatic absorbents for minimally invasive surgery.

CONTENTS
ACKNOWLEDGMENETIII
ABSTRACT (English)IV
ABSTRACT (Chinese)VI
CONTRIBUTIONVIII
LIST OF SCHEMESXVII
LIST OF FIGURESXVIII
CHARACTER 1 INTRODUCTION1
CHARACTER 2 LITERATURES REVIEW6
2.1 Preface6
2.1.1 The Introduction of Adhesive6
2.1.2 Conditions for Satisfactory Bonding7
2.1.3 Bonding Theories7
2.1.3.1 The mechanical interlock theory8
2.1.3.2 The adsorption theory8
2.1.3.3 The chemisorption theory9
2.1.3.4 The electrostatic theory9
2.1.3.5 The diffusion theory10
2.1.3.6 Bonding Theories The weak boundary layer theory11
2.2 The Theory of Adhesive11
2.2.1 Adsorption12
2.2.2 Chemisorption15
2.2.3 Mechanical Interlocking16
2.2.4 Diffusion18
2.2.5 Electrostatic19
2.3 Factors that influence the adhesion20
2.3.1 Wetting of the surface21
2.3.2 Surface treatment22
2.3.3 Stucture of the materials to be bonded33
2.3.4 Stucture of the joint35
2.4 Market of Gelatin Products and Application30
2.4.1 Edible Gelatins30
2.4.1.1 Confectionery31
2.4.1.2 Gelatin Desserts32
2.4.1.3 Gelatin in Meats34
2.4.1.4 Clarification of Beverages and Juices34
2.4.1.5 Special Dietary Uses35
2.4.2 Pharmaceutical Gelatins38
2.4.2.1 TwoPiece Hard Capsules39
2.4.2.2 Soft Elastic Gelatin Capsules41
2.4.2.3 Tablets42
2.4.2.4 Tablet Coating44
2.4.2.5 Suppositories45
2.4.2.6 Gelatin Emulsions46
2.4.2.7 Microencapsulation47
2.4.2.8 Absorbable Gelatin Sponge47
2.4.2.9 Absorbable Gelatin Film48
2.4.2.10 Pastilles and Troches48
2.4.2.11 Bacterial Growth Media48
2.4.3 Photographic Gelatins49
2.4.4 Technical Gelatins52
2.4.4.1 Coating and Sizing53
2.4.4.2 Paper Manufacture54
2.4.4.3 Printing Processes54
2.4.4.4 Protective Colloidal Applications55
2.4.4.5 Matches56
2.4.4.6 Coated Abrasives56
2.4.4.7 Adhesives56
2.4.4.8 Gelatin Films and Light Filters57
2.4.4.9 Cosmetics57
2.4.4.10 Microencapsulation58
CHARACTER 359
3.1 Experimental59
3.1.1 Materials59
3.1.2 Instruments60
3.1.3 A Model Reaction61
3.1.4 Synthesis of GlyBTHE61
3.1.5 Synthesis of GEBTHE62
3.1.6 Preparation of Photocurable Glue63
3.1.7 Photocuring63
3.1.8 Gel Content Determination64
3.1.9 Swelling Test64
3.1.10 The Trinitrobenzene Sulfonic Acid (TNBSA)65
3.2 Results and Discussions 66
3.2.1 Synthesis and Characterization of GlyBTHE67
3.2.2 Differential Scanning Calorimeter (DSC) Analysis68
3.2.3 Synthesis and Characterization of GEBTHE68
3.2.4 The Effect of the Concentration of GEBTHE Solution69
3.2.5 Gel Behaviors of Photoreactive Gelatin (GEBTHE)70
3.2.6 Swelling Behaviors of Photoreactive Gelatin (GEBTHE)71
3.2.7 Photosensitivity of GEBTHE71
3.2.8 Morphology of GEBTHE72
3.2.9 Dynamic of Photocrosslinking GEBTHE72
3.2.10 Tensile Properties of GEBTHE73
3.2.11 Swelling Ratio of GEBTHE74
3.2.12 Contact Angle of GEBTHE75
3.3 Conclusion76
CHARACTER 497
4.1 Experimental97
4.1.1 Chemicals and Instruments97
4.1.2 Synthesis of GEBTHE98
4.1.3 Preparation of Photocurable Glues99
4.1.4 The Gel Content Test99
4.1.5 The Contact Angle Test99
4.1.6 UVvis Spectra Analysis100
4.1.7 AFM Analysis100
4.1.8 SEM Morphology101
4.2 Results and Discussions102
4.2.1 Synthesis and Characterization of GEBTHE102
4.2.2 UV Photocuring Analysis102
4.23 Atomic Force Microscopy of GEBTHE104
4.2.4 Water Contact Angle Measurement106
4.2.5 SEM Morphology Observation106
4.2.6 Image Transfer Experiment107
4.3 Conclusion108
CHARACTER 5 SUMMARY119
REFERENCES121
APPENDIX128
VITA130

LIST OF SCHEME

SCHEME 1 The reaction of the preparation of GlyBTHE 78
SCHEME 2 The reaction of the preparation of GEBTHE 79


LIST OF FIGURES

(Chapter 3)
FIGURE 1 The comparison of FTIR spectra of (a)BTDA, (b)BTHE, (c)GlyBTHE and (d)glycine 80
FIGURE 2 The estimated and actual 1HNMR analysis of GlyBTHE 81
FIGURE 3 The DSC curve of GlyBTHE 82
FIGURE 4 FTIR spectra of BTDA and BTDAHEMA half ester intermediate 83
FIGURE 5 FTIR spectra of gelatin and unexposed GEBTHE 84
FIGURE 6 The TGA spectrum of GEBTHE 85
FIGURE 7 The gel content of different composition of GEBTHE 86
FIGURE 8 The different type of comparisons for (1)BTDA 0.004mole (2)BTDA 0.002mole 87
FIGURE 9 The degree of swelling of GEBTHE at different irradiated time in deionized water and saline 88
FIGURE 10 The degree of swelling changes with different exposure time of GEBTHE (20% GEBTHE) 89
FIGURE 11 The degree of swelling changes with different compositions 8%, 16%, 24%, 30% of GEBTHE (Irradiated 1 hr) 90
FIGURE 12 The weight of GEBTHE film changes with the irradiation time 91
FIGURE 13 The comparison of a gelatin mixed with BTHE and the GEBTHE (Absorbance Max. at 267 nm) 92
FIGURE 14 Tappingmode AFM topography of 20% GEBTHE irradiated film (1.5 mm) (Up left:100 um, up right: 5 um, down left: section line, down right, section analysis.) 93
FIGURE 15 The behavior of photoreactive gelatin (G3) with the increasing irradiated time 94
FIGURE 16 The dependency of gel content and swelling ratio on irradiated time (G3) 95
FIGURE 17 The effect of contact angle with different BTDA contained (G1, G2, G3 and G4 contained 0.005, 0.010, 0.015 and 0.020 mole BTDA individually.)96

(Chapter 4)
FIGURE 18 The 1HNMR of gelatin and gelatin based, photocurable gel, GEBTHE, illustrating their differences in the main functional groups110
FIGURE 19 The maximum absorbance of UVvis spectra of GEBTHE in three different wavelengths was 267 nm 111
FIGURE 20A Relationship between the maximum UV absorbance and the duration of irradiation. UV light of two different wavelengths were used to irradiate the GEBTHE 112
FIGURE 20B UVvis spectra of dilute GEBTHE solution upon irradiation with UV light as the exposure time and the maximum absorbance 113
FIGURE 21 Changes of UVlight absorptions of GEBTHE as a function of time 114
FIGURE 22 AFM section analysis of the surface of a GEBTHE membrane (365 nm for 3 min) 115
FIGURE 23 A comparison between AFM images of two GEBTHE membranes (20 %) 116
FIGURE 24 Scanning electron micrographs of (a) 5 wt%, (b) 10 wt% and (c) 20 wt% GEBTHE membranes illustrating the effect of gel content on the smoothness of the membrane surface 117
FIGURE 25 The photocuring and the image transfer pattern of 20 wt% GEBTHE 118

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