跳到主要內容

臺灣博碩士論文加值系統

(216.73.216.143) 您好!臺灣時間:2026/10/11 06:57
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:洪啟芳
研究生(外文):Chi-Fang Hung
論文名稱:硫化程度對一些多醣及寡糖之抗凝血性質之探討
論文名稱(外文):Degree of Sulfation of Some Polysaccharides and Oligosaccharides to Anticoagulant Properties
指導教授:段國仁段國仁引用關係
指導教授(外文):Kow-Jen Duan
學位類別:碩士
校院名稱:大同大學
系所名稱:生物工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:108
中文關鍵詞:抗凝血、麥芽寡醣、硫化程度、仙草凝膠、鹿角菜膠
外文關鍵詞:Anticoagulant、Maltooligosaccharides、Degree of sulfation、Hsian-tsao gel、Carrageenan
相關次數:
  • 被引用被引用:28
  • 點閱點閱:787
  • 評分評分:
  • 下載下載:73
  • 收藏至我的研究室書目清單書目收藏:0
硫化寡醣和硫化多醣可以抑制肝素酶、凝血酶和細胞間質金屬蛋白酶(matrix metalloproteinase)等蛋白酶,防止血液在血管中凝固,可封鎖血管增生(angiogenesis)的誘導因子,抑制腫瘤生長,以及防止風濕性關節炎和增生視網膜病等疾病,具有抗凝血的功效,用來研發替代現有的抗凝血藥物肝素(heparin)。本研究利用硫化的麥芽三、四、五、六、七糖,探討不同的硫化程度對抗凝血活性的影響。結果發現麥芽寡糖的硫化程度愈高,對活化部分凝血活素時間(activated partial thromboplastin time; APTT)代表的凝血機制內系統凝血路徑有較好的延遲效果,而高度硫化的麥芽四糖與麥芽五糖對代表凝血機制外系統凝血路徑的凝血酶原時間(prothrombin time; PT)有延遲的效果。此外,仙草多醣凝膠(Hsian-tsao gel)與鹿角菜膠(carrageenan)等本身具有抗凝血的功效,經過硫化處理後,其硫化的程度愈高,抗凝血的功效愈好。仙草多醣凝膠對APTT與PT均有較好的延遲效果;鹿角菜膠只對APTT有延遲凝血的效果,對PT則無。
Sulfated polysaccharides and oligosaccharides inhibit some protease as heparanase, thrombin and matrix metalloproteinase to prevent blood coagulation. Sulfated polysaccharides and oligosaccharides also inhibit angiogenesis inducing factor and tumorigenesis, and prevent some diseases as proliferative retinopathies and rheumatoid arthritis. Sulfated polysaccharides and oligosaccharides are developed to replace heparin (the traditional anticoagulant drug) according to their anticoagulant properties. In this research, we compared the degree of sulfation of sulfated maltotriose, maltotetraose, maltopentaose, maltohexaose, and maltoheptaose with their anticoagulant activity. The result shows that the higher degree of sulfation of sulfated maltooligosaccharides delayed activated partial thromboplastin time (APTT) longer, and the completely sulfated maltotetraose and maltopentaose have the ability to delay prothrombin time (PT). Sulfated maltooligosaccharides have better anticoagulant property in intrinsic pathway than in extrinsic pathway. Furthermore, hsian-tsao gel and carrageenan also have anticoagulant properties, and these gels have better anticoagulant properties with the higher degree of sulfation after sulfation of these gels. Hsian-tsao gel has the ability to delay APTT and PT, but carrageenan has the ability to delay APTT only.
ABSTRACT I
中文摘要 III
目錄 IV
圖目錄 VII
表目錄 IX
第一章 前言 1
第二章 文獻回顧 3
2.1血液與凝血機制 3
2.1.1血液的組成 3
2.1.2血小板的機能 6
2.1.3凝血機制(Mechanism of blood coagulation) 8
2.1.4凝血作用的測試 13
2.2抗凝血劑的介紹 15
2.2.1正常血管系統的防止凝血作用-血管內之抗凝血劑 15
2.2.2抗凝血劑(Heparinoids) 23
2.3麥芽寡糖的介紹 33
2.3.1澱粉(Starch) 33
2.3.2澱粉水解酵素 38
2.4植物多醣凝膠 43
2.4.1仙草多醣凝膠 43
2.4.2海藻多醣膠 45
第三章 材料與方法 49
3.1材料 49
3.1.1麥芽寡糖的製備 49
3.1.2硫化麥芽寡糖的硫化程度與抗凝血功效 49
3.2儀器與設備 52
3.3實驗方法 53
3.3.1麥芽寡糖的製備 53
3.3.2麥芽寡糖的分析 53
3.3.3麥芽寡糖的硫化 54
3.3.4植物多醣凝膠的萃取 54
3.3.5植物多醣凝膠的硫化 55
3.3.6硫化程度(Degree of Sulfation,DS.)的分析 56
3.3.7硫化麥芽寡糖與硫化多醣之抗凝血活性 58
第四章 結果與討論 64
4.1澱粉水解麥芽寡糖的抗凝血活性 64
4.1.1麥芽寡糖的製備與分析 64
4.1.2麥芽寡糖的硫化程度分析 67
4.1.3麥芽寡糖硫化後的抗凝血活性 69
4.1.4我力夠糖漿麥芽寡糖的分析 72
4.1.5我力夠糖漿麥芽寡糖的硫化程度分析 75
4.1.6我力夠糖漿麥芽寡糖硫化後的抗凝血活性 77
4.2標準麥芽寡糖的抗凝血活性 80
4.2.1標準麥芽寡糖的硫化程度分析 80
4.2.2標準麥芽寡糖硫化後的抗凝血活性 82
4.3仙草多醣凝膠的抗凝血活性 85
4.3.1仙草多醣凝膠的硫化程度分析 85
4.3.2仙草多醣凝膠的硫化與抗凝血活性 87
4.4鹿角菜膠的抗凝血活性 90
4.4.1鹿角菜膠的硫化程度分析 90
4.4.2鹿角菜膠的硫化與抗凝血活性 92
第五章 結論 95
參考文獻 97
王文憲編譯。1994。人體生理學。合記圖書出版社發行。
王應堯。1990。肝素引起之血小板減少症及血栓栓塞。國防醫學,10:6,558-561。
史宏財,許明仁。1994。仙草凝膠物質之萃取及其凝膠性質之研究。桃園區農業改良場研究報告,16: 1-9。
何敏夫。1993。血液學。合記圖書出版社發行。
李業英。1999。探討肝素溶液與生理食鹽水對於維持橈動脈導管通暢之成效。私立中山醫學院醫學研究所碩士論文。
林昇鋒編譯。1993。血液學概論。合記圖書出版社發行。
林孟賢和曾春典。1995。肝素及其在抗凝血治療上的應用。當代醫學,22:1,2-8。
陳明賢。2000。高溫長桿菌(Bacillus stearothermophilus 91)的分離及其所產高溫穩定澱粉酶純化及特性之研究。國立台灣海洋大學水產養殖所碩士論文。
陳國誠。1999。酵素工程學,3版,藝軒圖書出版社。25-28。
楊啟春,陳理宏,呂政義。1982。仙草凍凝膠機構之研究-以不同乙醇濃度沉澱仙草多醣膠質之凝膠性及其醣成分之組成。食品科學,9: 19-26。
葉曙著。1989。最新簡明病理學,正中書局。342-347。
蘇泉發,張玉麟,陳新源,陳逸文,李超群。1999,即時出血的高血壓性腦出血患者之電腦斷層血管造影表徵-例報告。慈濟醫學,11: 183-189。
Alban S. 1997. Carbohydrates with anticoagulant and antithrombotic properties In: Witczak Z.J., K.A. Nieforth, editors, Carbohydrates in drug design. New York: Marcel Dekker, 209-276.
Barbanti M., F. Calanni, M.R. Milani, E. Marchi, N. Semeraro, M. Colucci. 1993. Therapeutic effect of low molecular weight dermatan sulfate (Deamin 370) in rat venous thrombosis-evidence for an anticoagulant-independent mechanism. Thromb. Haemost.,69:147-151.
Bealin-Kelly F., Kelly C. T., Fogarty W. M. 1990. The a-amylase of the caldoactive bacterium Bacillus caldovelox. Biochem. Enzymol., 1: 149-158.
Bianchini P., Osima B., Parma B., Nader H. B., Dietrich C.P. 1982. Pharmacological activities of heparins obtained from different tissues: Enrichment of heparin fractions with high lipoprotein lipase, antithemolytic and anticoagulant activities by molecular sieving and antithrombin III affinity chromatography. J. Pharmacol. Exp. Ther., 220: 406-410.
Bianchini P., B. Osima, B. Parma, H.B. Nader, C.P. Dietrich. 1995. Lack of correlation between‘in vitro’and‘in vivo’antithrombotic activity of heparin fractions and related compounds. Heparan sulfate as an antithrombotic agent‘in vivo’.Thromb. Res., 39: 21-28.
Bienkowski M.J., H.E. Conrad. 1984. Kinetics of proteoheparan sulfate synthesis, secretion, endocytosis, and catabolism by a hepatocyte cell line. J. Biol. Chem., 259: 12989-12996.
Bradbrook I.D., H.N. Magnani, H.C. Moelker, P.J. Morrison, J. Robinson, J. Rogers, R.G. Spector, T. Van Dinther, H. Wijnand. 1987. ORG 10172: A low molecular weight heparinoid anticoagulant with a long half-life in man. Br. J. Clin. Pharmacol.,23: 667-675.
Caceres P.J., M.J. Carlucci, E.B. Damonte, B. Matsuhiro, E.A. Zuniga. 2000. Carrageenans from chilean samples of Stenogramme interrupta (Phyllophoraceae): structure analysis and biological activity. Phytochemistry. 53: 81-86.
Carlucci M.J., C.A. Pujol, M. Ciancia, M.D. Noseda, M.C. Matulewicz, E.B. Damonte, A.S. Cerezo. 1997. Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: correlation between structure and biological activity. International Journal of Biological Macromolecules. 20: 97-105.
Casu B. 1991. Structural features and binding properties of chondroitin sulfastes, dermatan sulfate, and heparan sulfate. Semin. Thromb. Hemost.,17 (suppl 1): 9-14.
Chevolot L., B. Mulloy, J. Ratiscol, A. Foucault, S. Colliec-Jouault. 2001. A disaccharide repeat unit is the major structure in fucoidans from two species of brown algae. Carbohydrate Research. 330: 529-535.
Dawes J. 1998. Measurement of the affinities of heparins, naturally occurring GAGs, and other sulfated polymers for antithrombin III and thrombin. Anal. Biochem.,174: 177-186.
De Clercq E. 1990. Selective virus inhibitors. Microbiologica.,13:165-178.
Dol F., M. Petitou, J. Choay, P. Sie, G. Houin, B. Boneu. 1989. Pharmacological properties of dermatan sulfate, of a low molecular weight dermatan sulfate (LMDS) and of two oversulfated derivatives. Folia Haematol Int Mag Klin Morphol Blutforsch.,116:851-857.
Edward M., E.M. Conway, S. Pollefeyt, D. Collen, M. Steiner-Mosonyi. 1997. Blood.,89:652.
Fareed J., D. Hoppensteadt, W. Jeske, J.M. Walenga. 1993. An overview of nonheparin glycosaminoglycans as antithrombotic agents. In: Poller L,ed.Recent Advances in Blood Coagulation. London: Churchilll Livingstone.,169-187.
Fransson L.A., B. Havsmark. 1982. Interaction of heparin and heparan sulfate with low-density lipoproteins. Inc J. Bio. Macrom., 4 : 73-78.
Fransson L.A., B.G. Johannson. 1981. Interaction of heparin and heparan sulfate with thrombin. Int J. Bio. Macrom., 3: 25-30.
Fogarty W.M., F. Bealin-Kelly, C.T. Kelly, E.M. Doyle. 1991. A novel maltohexaose-forming a-amylase from Bacillus caldovelox : patterns and mechanisms of action. Appl. Microbiol. Biotechnol., 36:184-189.
Guiseley K.B. 1978. Some novel methods and results in the sulfation polysaccharides. In: Schweiger, R.G., ed. Carbohydrate Sulfates. Washington DC; American Chemical Society.148:162.
Greinacher A., S. Alban, V. Dummel, G. Franz, C. Mueller-Eckhardt. 1995. Characterization of the structural requirements for a carbohydrate based anticoagulent with a reduced risk of inducing the immunological type of heparin-associated thrombocytopenia. Thrombo. Haemost.,75: 886-892.
Hayashi T., T. Akiba, K. Horikoshi. 1998. Production and purification of new maltohexaose-forming amylase from alkalophilic Bacillus sp. H-167. Agric. Biol.Chem., 52: 443-448.
Hoppensteadt D., J. Walenga, J. Fareed. 1991. Effect of dermatan sulfate and heparan sulfate on platelet activity compared to heparin.Semin Thromb Hemost.,17(suppl 1): 60-64.
Hubbard A.R., C.A. Jenning, T.W. Barrowcliffe. 1984. Anticoagulant properties in vitro of heparan sulfates. Thromb Res.,35: 567-576.
Jaques L.B. 1985. Heparin: An old drug with a new paradigm (Part A). Hamostaseologie., 5 : 88-92.
Kamide K., M. Saito. 1987. Cellulose and cellulose derivatives: recent advances in physical chemistry. Adv. Polym. Sci., 83:1-56.
Kent M., Van De Graaff. 1990. Stuart ir a fox,“ Circulatory system: blood”, Concepts of Human Anatomy and Physiology., 20: 531-542.
Klauser R.J., E. Meinetsberger, W. Raake. 1991. Biochemical studies on sulfated lactobionic acid amides. Semin. Thromb. Hemost.,17: 118-125.
Lindahl U., M. Hook. 1978. Glycosaminoglycans and their binding to biological macromolecular. Ann. Rev. Biochem.,47: 385-417.
Mamdouh B.A., M. Monia, B. Samir. 1999. A thermostable a-amylase producing maltohexaose from a new isolated Bacilllus sp. US100: study of activity and molecular cloning of the corresponding gene. Enzyme and Microbial Technology.,24: 584-598.
Marcum J.A., R.D. Rosenberg. 1987. Anticoagulantly acyive heparan sulfate proteoglycan and the vascular endothelium. Semin. Thromb. Hemost.,13: 464-474.
Marroufi R.M., J. Tapon-Bretaudiere, K. Mardiguian, C. Sternberg, M.D. Dautzenberg, A.M. Fischer. 1990. Influence of the oversulfation method and the degree of sulfation on the anticoagulant properties of dermatan sulfate derivative. Thromb. Haemost.,59:749-758.
Mascellani G., L. Liverani, P. Bianchini, B. Parma, G. Torri, M. Guerrini, B. Casu. 1993. Structure and contribution of the heparin cofactor II-mediated inhibition of thrombin of naturally oversulphated sequences of germatan sulphate. Biochem. J., 296: 639-648.
Merton R.E., D.P. Thomas. 1987. Experimental studies on the relative efficacy of dermatan sulphate and heparin as antithrombotic agents. Thromb. Haemost.,58: 839-842.
Minix R., V.M. Doctor. 1997. Interaction of fucoidan with proteases and inhibitors of coagulation and fibrinolysis. Thromb. Res.,87: 419-429.
Mulloy B., P.A.S. Mourao, E. Gray. 2000. Structure/function studies of anticoagulant sulphated polysaccharides using NMR. Journal of Biotechnology, 77: 123-135.
Murayama H., J. Nakajima and I. Yamamoto. 1987. A study on the anticoagulant and fibrinolytic activities of a crude fucoidan from the edible brown seaweed Laminaria religiosa, with special reference to its inhibitory effect on the growth of sarcoma-180 ascites cells subcutaneously implanted into mice. Kitasato Arch. of Exp. Med. 60(3): 105-121.
Muzzarelli R.A.A., F. Tanfani, M. Emannuelli, D.P. Pace, E. Chiurazzi, M. Piani. 1984. Sulfated N-(carboxymethyl)chitosan: novel blood anticoagulants. Carbohydr Res.126: 225-231.
Nagaswas K., H. Harada, S. Hayashi, T. Misawa. 1972. Sulfation of dextran with piperidine-N-sulfonic acid. Carbohydr. Res.,21:420-426.
Nagase H., K. Enjyoji, K. Minamiguchi, K.T. Kitazato, H. Saito, H. Kato. 1995. Depolymerized holothurian glycosaminoglycan with novel anticoagulant actions:Antithrombin III- and heparin cofactor II-independent inhibition of factor X activation by factor IX-factor VIIIa complex and heparin cofactor II-dependent inhibition of thrombin.Blood.,85:1527-1534.
Nishimura S.I., S. Tokura, W. Okiei, O. Somorin. 1986. Inhibition of the hydrolytic activity of thrombin by chitin heparinoids. Caebohydr. Res.,156: 286-292.
Norman B.E. 1979. The application of polysaccharide degrading enzymes in the starch industry.In:Microbial polysaccharide and polysaccharases (Berkeley, R. C. W., Gooday, G.W., and Ellwood, D.C. eds.) Academic. Press., London., 339-367.
Ofosu F.A., M.R. Buchanan, N. Anvari, L.M. Smith, M.A. Blajchmam. 1989. Plasma anticoagulant mechanism of heparin, heparan sulfate, and dermatan sulfate. Ann New York Acad Sci., 556:123-131.
Ofosu F.A., J. Choay, N. Anavri, L.M. Smith, M.A. Blajchmam. 1990. Inhibition of factor X and factor V activation by dermatan sulfate and a pentasaccharide with high affinity for antithrombin II in human plasma. Eur J Biochem.193: 485-493.
Parish C.R., C. Freeman, K.J. Brown, D.J. Francis, W.B. Cowden. 1999. Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. Cancer Research. 59: 3433-3441.
Perlin A.S., F. Sauriol, C. Caranobe, M. Pentitou, J.C. Lormeau, P. Sie, J. Choay. 1988. Standard heparin enhances the antithrombotic activity of dermatan sulfate in the rabbit but CY216 dose not. Thromb. Haemost.,59: 295-298.
Ricketts C.R. 1952. Dextran sulphate - a synthetic analogue of heparin. Biochem.,51: 129-133.
Saivin S., F. Dol, C. Caranobe, M. Petitou, J.C. Lormeau, P. Sie, G. Houin, B. Boneu. 1992. Influence of molecular weight upon the anticoagulant and pharmacokinetic properties of dermatan sulfate in the rabbit. Thromb. Res., 66: 527-535.
Santoro F.M., R. Alvarez, F. Fussi. 1992. Pharmacological profile of a native dermatan sulfate. Thromb. Res., 67: 201-211.
Sie P., F. Ofosu, F. Fernandez, M.R. Buchanan, M. Petitou, B. Boneu. 1986. Respective role of antithrombin III and heparin cofactor II in vitro anticoagulant effect of heparin and of various sulphated polysaccharides. Br. J. Haematol., 64:707-714.
Sie P., D. Dupouy, C. Caranobe, M. Petitou, B. Boneu. 1993. Antithrombotic properties of a dermatan sulfate hexadecasaccharide fractionated by affinity for heparin cofactor II. Blood.,81: 1771-1777.
Stryer L. 1995. Biochemistry, 4th edition, W. H. Freeman and Company.
Takasaki Y. 1982. Production of maltohexaose by a-amylase from Bacillus circulans G-6. Agric. Biol. Chem., 46: 1539-1547.
Van Ryn-McKennaa J., F.A. Ofosu, E. Gray, J. Hirsh, M.R. Buchanan. 1989. Effects of dermatan sulfate and heparin on inhibition of thrombus growth in vivo. Ann New York Acad. Sci., 556: 304-312.
Vihinen M., P. Ollikka, J. Niskanen, P. Meyer, I. Suominen, M. Krap, L. Holm. 1990. Knowles, J., Mantsala, P., Site-directed mutagenesis of a thermostable a-amylase from bacillus stearothermophilus: putative role of three conserved residues. J. Biochem.,107: 267-272.
Wall D., S. Douglas, V. Ferro, W. Cowden and C. Parish. 2001. Characterisation of the anticoagulant properties of a range of structurally diverse sulfated oligosaccharides. Thrombosis Research. 103: 325-335.
Whistler R.L., W.W. Spencer. 1961. Preparation and properties of several polysaccharide sulfates. Arch. Biochem. Biophys., 95: 36-41.
Woo G.J., J.D. McCord. 1994. Bioconversion of starches into maltotetraose using Pseudomonas stutzeri maltotetraohydrolase in a membrane recyclic bioreactor: effect of multiple enzyme systems and mass balance study. Enzyme. Microb. Technol., 16: 1016-1020.
Yoshigi N., T. Chikano, M. Kamimura. 1985. Characterization of a maltopentaose-producing bacterium and its cultural conditions. Agric. Biol. Chem., 49:2379-2384.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top