성장인자/키토산이 담지된 온도감응성 하이드로젤의 유착방지제로서의 응용

박준규; 나재운; 최창용; Jun-Kyu Park; Jae-Woon Nah; Changyong Choi

Polymer(Korea), Vol.39, No.3, 480-486, May, 2015

DOI10.7317/pk.2015.39.3.480 Export Citation

성장인자/키토산이 담지된 온도감응성 하이드로젤의 유착방지제로서의 응용

Thermosensitive Chitosan-based Hydrogel with Growth Factor as Adhesion Barrier

박준규^{1, 2}, 나재운 ^{2, †}, 최창용 ^{2, †}

¹(주)바이오알파
²순천대학교 공과대학 고분자공학과

Jun-Kyu Park^{1, 2}, Jae-Woon Nah^{2, †}, and Changyong Choi^{2, †}

¹Bioalpha Co. Ltd., Jangseong, Jeonnam 515-893, Korea
²Department of Polymer Science and Engineering, Sunchon National University, Jeonnam 540-742, Korea

E-mail:,

초록

조직과 장기 유착은 외과적 수술 후 부작용으로 자주 발생된다. 이러한 조직 유착을 방지하기 위하여 유착부위에 장벽을 형성하여 장기 유착을 방지할 수 있는 온도감응성 하이드로젤 유착방지제를 제조하고자하였다. 폴록사머, 키토산과 표피성장인자를 가지고 온도감응성 키토산 하이드로젤을 제조하였다. 제조한 키토산 하이드로젤은 인체 내 온도와 유사한 35 oC에서 졸-젤 전이현상을 보였고, 1분 이내에 빠르게 젤화되었다. 키토산 하이드로젤은 표피성장인자를 7일 동안 천천히 방출하였고, 마우스모델에서 평가한 결과 조직 유착 방지를 효과적으로 하는 것을 확인하였다. 온도 감응성과 항균성을 갖는 키토산 하이드로젤이 장기 부착의 증가와 표피성장인자를 천천히 방출하는 유착방지제로서 유용하게 사용될 수 있다.

The adhesion of tissue and organ occur with frequency after surgery. Theomosensitive hydrogel was prepared from poloxamer/chitosan/epidermal growth factor as adhesion barrier agent. The prepared hydrogel showed sol-gel transition temperatures around human temperature and gelation temperature was the faster within 1 min. The hydrogel sustained the release of epidermal grow factor during 7 days. The hydrogel was highly effective for the prevention of tissue and organ adhesion in rat model. The thermosensitive and antibacterial chitosan hydrogel can be useful to consider the anti-adhesion barrier with increased adhesion of organ and sustained release of epidermal growth factor.

Keywords:poloxamer;chitosan;tissue anti-adhesion;hydrogel;epidermal growth factor

[References]

Yang HY, Suh KS, Youn YK, Kim SW, Kim SJ, Lee KU, Park YH, J. Korean Surg. Soc., 52, 335 (1997)
Lee WJ, Moon BI, Park JB, Kim IM, You BO, J. Korean Surg. Soc., 49, 192 (1995)
Falk K, Bjorquist P, Stromqvist M, Holmdahl L, Br. J. Surg., 8, 286 (2001)
Shim HS, Lee YW, Lee YM, Oh YH, Kwon SW, Kim JH, Sohn SK, J. Korean Sur. Soc., 63, 179 (2002)
Hurme M, Katevuo K, Nykvist F, Aalto T, Alaranta H, Einola S, Acta Radiol., 32, 286 (1991)
Attwood D, Collett JH, Tait CJ, Int. J. Pharm., 126, 25 (1985)
Ranade VV, Cannon JB, Drug Delivery Systems, CRC Press, London, 2011. (2011)
Brine CJ, Austin PR, Comp. Biochem. Physiol., B: Comp. Biochem., 69, 283 (1981)
Shahi F, Arachchi JKV, Jeon YJ, Trends Food Sci. Technol., 10, 37 (1999)
Evans EE, Kent SP, J. Histochem. Cytochem., 10, 24 (1962)
Tokura S, Azuma I, Chitin Derivatives in Life Science, Japan Soc. Chitin, Sapporo, 1992. (1992)
Ikeda I, Sugano M, Yoshida K, Sasaki E, Iwamoto Y, Hatano K, J. Agric. Food Chem., 41, 431 (1993)
Muzzarelli RAA, Lough C, Emanuelli M, Carbohydr. Res., 164, 433 (1987)
Na DH, Youn YS, Lee IB, Park EJ, Park CJ, Lee KC, Pharm. Dev. Technol., 11, 513 (2006)
Goodlad RA, Wilson TG, Lenton W, Gregory H, Mccullagh KG, Wright NA, Experientia, 41, 1161 (1985)
Bragg LE, Hollingsed TC, Thompson JS, J. Parenter. Enteral Nutr., 14, 283 (1990)
Reim M, Kehrer T, Lund M, Ophthalmologica, 197, 179 (1988)
Jaacobi Y, Israel AA, Goldberg EP, J. Surg. Res., 55, 422 (1993)
Luciano AA, Hauser KS, Benda J, Am. J. Obstet. Gynecol., 146, 88 (1983)
Schmolka IR, J. Am. Oil Chem. Soc., 54, 110 (1977)
Wanka G, Hoffmann H, Ulbricht W, Macromolecules, 27(15), 4145 (1994)
Oh SH, Kim JK, Song KS, Noh SM, Ghil SH, Yuk SH, Lee JH, J. Biomed. Mater. Res., 72A, 306 (2005)
Edsman K, Carlfors J, Petersson R, Eur. J. Pharm. Sci., 6, 105 (1998)
Chen YY, Wu HC, Sun JS, Dong GC, Wang TW, Langmuir, 29(11), 3721 (2013)
Jung HH, Park K, Han DK, J. Control. Release, 147, 84 (2010)
Prudhomme RK, Wu GW, Schneider DK, Langmuir, 12(20), 4651 (1996)
Park JK, Lee KJ, Son DH, Choi C, Jang MK, Nah JW, J. Chitin Chitosan, 16, 45 (2011)
Chen J, Jhou R, Li L, Li B, Zhang X, Su J, Molecules, 18, 12415 (2013)
Wei G, Xu H, Ding PT, Li SM, Zheng JM, J. Control. Release, 83, 65 (2002)
Ellis H, Harrison W, Hugh TB, Br. J. Surg., 52, 471 (1965)
Kim MH, Park SC, Jang MK, Nah JW, Hahm KS, Park Y, J. Chitin Chitosan, 13, 1 (2008)
Gratieri T, Gelfuso GM, Rocha EM, Sarmoto VH, Freitas OD, Lopez RFV, Eur. J. Pharmacol. Biopharmaceut., 75, 186 (2010)

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[3] Falk K, Bjorquist P, Stromqvist M, Holmdahl L, Br. J. Surg., 8, 286 (2001)

[4] Shim HS, Lee YW, Lee YM, Oh YH, Kwon SW, Kim JH, Sohn SK, J. Korean Sur. Soc., 63, 179 (2002)

[5] Hurme M, Katevuo K, Nykvist F, Aalto T, Alaranta H, Einola S, Acta Radiol., 32, 286 (1991)

[6] Attwood D, Collett JH, Tait CJ, Int. J. Pharm., 126, 25 (1985)

[7] Ranade VV, Cannon JB, Drug Delivery Systems, CRC Press, London, 2011. (2011)

[8] Brine CJ, Austin PR, Comp. Biochem. Physiol., B: Comp. Biochem., 69, 283 (1981)

[9] Shahi F, Arachchi JKV, Jeon YJ, Trends Food Sci. Technol., 10, 37 (1999)

[10] Evans EE, Kent SP, J. Histochem. Cytochem., 10, 24 (1962)

[11] Tokura S, Azuma I, Chitin Derivatives in Life Science, Japan Soc. Chitin, Sapporo, 1992. (1992)

[12] Ikeda I, Sugano M, Yoshida K, Sasaki E, Iwamoto Y, Hatano K, J. Agric. Food Chem., 41, 431 (1993)

[13] Muzzarelli RAA, Lough C, Emanuelli M, Carbohydr. Res., 164, 433 (1987)

[14] Na DH, Youn YS, Lee IB, Park EJ, Park CJ, Lee KC, Pharm. Dev. Technol., 11, 513 (2006)

[15] Goodlad RA, Wilson TG, Lenton W, Gregory H, Mccullagh KG, Wright NA, Experientia, 41, 1161 (1985)

[16] Bragg LE, Hollingsed TC, Thompson JS, J. Parenter. Enteral Nutr., 14, 283 (1990)

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[18] Jaacobi Y, Israel AA, Goldberg EP, J. Surg. Res., 55, 422 (1993)

[19] Luciano AA, Hauser KS, Benda J, Am. J. Obstet. Gynecol., 146, 88 (1983)

[20] Schmolka IR, J. Am. Oil Chem. Soc., 54, 110 (1977)

[21] Wanka G, Hoffmann H, Ulbricht W, Macromolecules, 27(15), 4145 (1994)

[22] Oh SH, Kim JK, Song KS, Noh SM, Ghil SH, Yuk SH, Lee JH, J. Biomed. Mater. Res., 72A, 306 (2005)

[23] Edsman K, Carlfors J, Petersson R, Eur. J. Pharm. Sci., 6, 105 (1998)

[24] Chen YY, Wu HC, Sun JS, Dong GC, Wang TW, Langmuir, 29(11), 3721 (2013)

[25] Jung HH, Park K, Han DK, J. Control. Release, 147, 84 (2010)

[26] Prudhomme RK, Wu GW, Schneider DK, Langmuir, 12(20), 4651 (1996)

[27] Park JK, Lee KJ, Son DH, Choi C, Jang MK, Nah JW, J. Chitin Chitosan, 16, 45 (2011)

[28] Chen J, Jhou R, Li L, Li B, Zhang X, Su J, Molecules, 18, 12415 (2013)

[29] Wei G, Xu H, Ding PT, Li SM, Zheng JM, J. Control. Release, 83, 65 (2002)

[30] Ellis H, Harrison W, Hugh TB, Br. J. Surg., 52, 471 (1965)

[31] Kim MH, Park SC, Jang MK, Nah JW, Hahm KS, Park Y, J. Chitin Chitosan, 13, 1 (2008)

[32] Gratieri T, Gelfuso GM, Rocha EM, Sarmoto VH, Freitas OD, Lopez RFV, Eur. J. Pharmacol. Biopharmaceut., 75, 186 (2010)