솔-젤 법을 이용한 유기-무기 Hybrid 고분자 네트웍의 제조와 헤파린의 고정화

김철희; 김은경; 진인주; 박기동; 김영하

Polymer(Korea), Vol.19, No.2, 240-246, March, 1995

Export Citation

솔-젤 법을 이용한 유기-무기 Hybrid 고분자 네트웍의 제조와 헤파린의 고정화

Heparin Immobilization on or into Organic-Inorganic Hybrid Polymeric Network Prepared by Sol-Gel Method

김철희, 김은경, 진인주, 박기동, 김영하

초록

1,4-Butanediol을 3-isocyanatopropyltriethoxysilane과 반응시켜 솔-젤 프리커서 화합물인 (EtO)₃Si(CH₂)₃NHCO₂(CH₂)₄O₂CNH(CH₂)₃Si(OEt)₃ (1)을 합성하고 솔-젤 반응을 이용하여 우레탄 작용기를 갖는 유기-무기 hybrid 고분자 네트웍을 제조하였다. 제조된 네트웍의 축합도 (degree of condensation)는 solid state CP MAS ²⁹Si-NMR 스펙트럼으로부터 약 80%로 분석되었다. 솔-젤 매트릭스 표면에 존재하는 우레탄기와 hexamethylene diisocyanate (HMDI)를 반응시켜 allophanate 형성에 의한 커플링으로 매트릭스 표면에 NCO기를 도입한 후 헤파린의 -OH, 또는 -NH₂와의 반응으로 헤파린을 네트웍의 표면에 고정화하였다. 헤파린을 솔-젤 매트릭스 내부에 고정화하기 위하여는 프리커서 1을 헤파린의 존재 하에서 젤화 (gellation) 하였다. 헤파린의 활동도(activity)는 APTT (activated partial thromboplastin time) 방법으로 측정하였는데, 네트웍 표면에 고정화된 경우는 2.9%, 내부에 고정화된 경우는 1.6%의 활동도를 각각 나타내었다.

A sol-gel precursor, (EtO)₃Si(CH₂)₃NHCO₂(CH₂)₄O₂CNH(CH₂)₃Si(OEt)₃ (1), was synthesized by the reaction of 1,4-butanediol and 3-isocyanatopropyltriethoxysilane. It was then sol-gel polymerized to produce an organic-inorganic hybrid network with urethane functionalities. The degree of condensation of the network was measured to be around 80% by solid state CP MAS ²⁹Si-NMR spectroscopy. NCO groups were introduced on the network surface through coupling by allophanate formation between hexamethylene diisocyanate and urethane functionalities on the gel surface. Heparin was immobilized on the surface of matrix by reacting -OH or -NH₂ of heparin with the surface NCO groups. On the other hand, heparin immobilization inside the matrix was carried out by the gellatlon of precursor 1 in the presence of heparin. Heparin activities were determined to be 2.9% on the surface and 1.6% in the matrix by the activated partial thromboplastin time (APTT) method.

Keywords:sol-gel;organic-inorganic hybrid polymers;heparin immobilization

[References]

Reuter H, Adv. Mater., 3(5), 258 (1991)
Brinker CJ, Scherer GW, "Sol-Gel Science, Academic Press, London (1990)
Gesser HD, Goswami PC, Chem. Rev., 89, 765 (1989)
Klein LC, "Sol-Gel Technology for Thin Films, Fibers, Preforms, Electronics, and Specialty Shapes," Noyes, Park Ridge, NJ (1988)
Corriu RJP, Moreau JJE, Thepot P, Man MWC, Chem. Mater., 4, 1217 (1992)
Mackenzie JD, Polym. Prepr., 70, 380 (1994)
Huang HH, Orler B, Wilkes GL, Macromolecules, 20, 1322 (1987)
Coltrain BK, Landry CJT, O'Reilly JM, Chamberlain AM, Rakes GA, SEdita JS, Kelts LW, Landry MR, Long VK, Chem. Mater., 5, 1445 (1993)
Novak BM, Adv. Mater., 5, 442 (1993)
Dave BC, Dunn B, Valentine JS, Zink JI, Anal. Chem., 66(22), 1120 (1994)
Avnir D, Braun S, Lev O, Ottolenghi M, Chem. Mater., 6, 1605 (1994)
Yoshinga K, Kito T, Yanaye M, J. Appl. Polym. Sci., 41, 1443 (1990)
Ellerby LM, Nishida CR, Nishida F, Yamanaka SA, Dunn B, Valentine JS, Zink JI, Science, 255, 1113 (1992)
Wu S, Ellerby LM, Cohan JS, Dunn B, El-Sayed MA, Valentine JS, Zink JI, Chem. Mater., 5, 115 (1993)
Audebert P, Demaille C, Sanchez C, Chem. Mater., 5, 911 (1993)
Johnson P, Whateley TL, J. Colloid Interface Sci., 37(3), 557 (1971)
Braun S, Rappoport S, Zusman R, Avnir D, Ottolenghi M, Mater. Lett., 10, 1 (1990)
Tatsu Y, Yamashita K, Yamaguchi M, Yamamura S, Yamamoto H, Yoshikawa S, Chem. Lett., 1615 (1992)
Perrin DD, Armarego WLF, "Purification of Laboratory Chemicals," Pergamon Press, New York (1988)
Park KD, Okano T, Nojiri C, Kim SW, J. Biomed. Mater. Res., 22, 977 (1988)
Shea KJ, Loy DA, Webster OJ, J. Am. Chem. Soc., 114, 6700 (1992)
Hepburn C, "Polyurethane Elastomers," p. 280, Applied Science Publishers, New York (1982)
Smith PK, Mallia AK, Hermanson GT, Anal. Biochem., 109, 466 (1980)

[Referenced By]

[1] Reuter H, Adv. Mater., 3(5), 258 (1991)

[2] Brinker CJ, Scherer GW, "Sol-Gel Science, Academic Press, London (1990)

[3] Gesser HD, Goswami PC, Chem. Rev., 89, 765 (1989)

[4] Klein LC, "Sol-Gel Technology for Thin Films, Fibers, Preforms, Electronics, and Specialty Shapes," Noyes, Park Ridge, NJ (1988)

[5] Corriu RJP, Moreau JJE, Thepot P, Man MWC, Chem. Mater., 4, 1217 (1992)

[6] Mackenzie JD, Polym. Prepr., 70, 380 (1994)

[7] Huang HH, Orler B, Wilkes GL, Macromolecules, 20, 1322 (1987)

[8] Coltrain BK, Landry CJT, O'Reilly JM, Chamberlain AM, Rakes GA, SEdita JS, Kelts LW, Landry MR, Long VK, Chem. Mater., 5, 1445 (1993)

[9] Novak BM, Adv. Mater., 5, 442 (1993)

[10] Dave BC, Dunn B, Valentine JS, Zink JI, Anal. Chem., 66(22), 1120 (1994)

[11] Avnir D, Braun S, Lev O, Ottolenghi M, Chem. Mater., 6, 1605 (1994)

[12] Yoshinga K, Kito T, Yanaye M, J. Appl. Polym. Sci., 41, 1443 (1990)

[13] Ellerby LM, Nishida CR, Nishida F, Yamanaka SA, Dunn B, Valentine JS, Zink JI, Science, 255, 1113 (1992)

[14] Wu S, Ellerby LM, Cohan JS, Dunn B, El-Sayed MA, Valentine JS, Zink JI, Chem. Mater., 5, 115 (1993)

[15] Audebert P, Demaille C, Sanchez C, Chem. Mater., 5, 911 (1993)

[16] Johnson P, Whateley TL, J. Colloid Interface Sci., 37(3), 557 (1971)

[17] Braun S, Rappoport S, Zusman R, Avnir D, Ottolenghi M, Mater. Lett., 10, 1 (1990)

[18] Tatsu Y, Yamashita K, Yamaguchi M, Yamamura S, Yamamoto H, Yoshikawa S, Chem. Lett., 1615 (1992)

[19] Perrin DD, Armarego WLF, "Purification of Laboratory Chemicals," Pergamon Press, New York (1988)

[20] Park KD, Okano T, Nojiri C, Kim SW, J. Biomed. Mater. Res., 22, 977 (1988)

[21] Shea KJ, Loy DA, Webster OJ, J. Am. Chem. Soc., 114, 6700 (1992)

[22] Hepburn C, "Polyurethane Elastomers," p. 280, Applied Science Publishers, New York (1982)

[23] Smith PK, Mallia AK, Hermanson GT, Anal. Biochem., 109, 466 (1980)