무채혈 혈당 측정시스템의 Patch Sensor용 수화젤의 합성 및 생체적합성에 관한 연구

권정우; 김동철; 윤인준; 정윤나; 정지영; 황인식; Jeong Woo Kwon; Dong Chul Kim; In Joon Yoon; Yoon Na Jeong; Ji Young Jeong; In Sik Hwang

Polymer(Korea), Vol.33, No.2, 111-117, March, 2009

Export Citation

무채혈 혈당 측정시스템의 Patch Sensor용 수화젤의 합성 및 생체적합성에 관한 연구

Synthesis and Biocompatibility Study of Hydrogel for Patch Sensor in Non-invasive Glucose Monitoring System

권정우^†, 김동철, 윤인준, 정윤나, 정지영, 황인식

케이엠에이치(주) R&D 센터

Jeong Woo Kwon^†, Dong Chul Kim, In Joon Yoon, Yoon Na Jeong, Ji Young Jeong, and In Sik Hwang

R&D Center, KMH Co., Ltd., Anyang Megavalley 4th floor,799 Gwanyang-dong, Dongan-gu, Anyang-si, Gyeonggi-do 431-060, Korea

E-mail:

초록

본 연구를 통해 역이온 영동(reverse iontophoresis)을 이용한 무채혈 혈당 측정시스템의 patch sensor에 사용되는 효소 고정형 수화젤의 생체적합성 여부를 확인하고자 하였다. 아크릴레이트 계열의 단량체를 사용하여 일정한 unit의 효소가 고정된 수화젤을 합성하였다. 합성된 수화젤의 물성분석을 위해 FT-IR spectrometer를 이용하여 구조분석을 하고 DSC를 이용하여 열적 안정성을 확인하였다. 또한, UV-Vis spectrophotometer를 이용하여 표준품대비 50% 이상의 효소 활성도를 확인하였다. 표면의 효소 고정화 확인을 위해 SEM을 이용하여 확인한 결과 효소가 고정화되어 있음을 확인하였다. 수화젤은 환자의 피부에 직접적으로 접촉됨으로써 접촉 시 무해성을 평가하기 위하여, ISO-10993에 의하여 세포독성(cytotoxicity), 피내반응(intracutaneous reactivity), 피부자극(skin irritation) 및 감작성(maximization sensitization) 시험을 실시하였고 이를 통해 생체적합성이 우수하다는 것을 확인하였다.

This study aims to verify for humans the suitability of the enzyme-fixed hydrogel used for the patch sensor of the blood sugar testing system without blood sampling, which utilizes reverse iontophoresis. Using acrylate monomers, hydrogel was synthesized to which a certain unit of enzyme is fixed. In order to analyze the material property of the synthesized hydrogel, a structural analysis was performed using FT-IR spectroscopy, while the DSC was used to verify the thermal stability. In addition, with the UV-Vis spectrophotometer, it was verified that the degree of active enzyme is at least 50% greater than the standard product. The SEM was used to verify secure fixation of the enzyme onto the surface. As a result, it was observed that the enzyme is successfully fixed to the surface. Since the hydrogel makes direct contact with a patient’s skin, it is essential to evaluate the toxicity when making direct contact with the skin. For that purpose, various sets of tests were undertaken according to the ISO 10993－cytotoxicity, intracutaneous reactivity, skin irritation test and maximization sensitization. Consequently, it was successfully verified that the enzyme-fixed hydrogel have bioavailability.

Keywords:hydrogel;glucose;GluCall;iontophoresis;non-invasive.

[References]

Choi JH, Park BH, Han YA, Kim SJ, Lim JO, Polym.(Korea), 28(1), 86 (2004)
Kwon SK, Polym.(Korea), 18(6), 1055 (1994)
Kurnik RT, Berner B, Tamada J, Potts RO, J. Electrochem. Soc., 145(12), 4119 (1998)
Jung DY, Magda JJ, Han IS, Macromolecules, 33(9), 3332 (2000)
Park YM, Kim US, Sung YK, Polym.(Korea), 15(3), 356 (1991)
Tierney M, Tamada J, Potts R, Biosens. Bioelectron., 16, 621 (2001)
Miyata T, Uragami T, Nakamae K, Adv. Drug Deliver. Rev., 54, 79 (2002)
Seidel JM, Malmoge SM, Material Research, 3, 79 (2000)
Garrett Q, Laycock B, Garrett R, Invest. Ophth. Vis. Sci., 41, 1687 (2000)
Sack R, Jones B, Antignani A, Libow R, Harvey H, Invest. Ophth. Vis. Sci., 28, 842 (1987)
Garrett Q, Chatelier R, Griesser H, Milthorpe B, Biomaterials, 19, 2175 (1998)
Castillo E, Koenig J, Anderson J, Lo J, Biomaterials, 6, 338 (1985)
Megan SL, Martina H, Stenzelb H, Simmonsa A, Milthorpea BK, Biomaterials, 27, 1341 (2006)
Ito T, Hioki T, Yamaguchi T, Shinbo T, Nakao S, Kimura S, J. Am. Chem. Soc., 124(26), 7840 (2002)
Traian VC, Constable IJ, Crawford GJ, Vijayasekaran S, Thompson DE, Chen YC, Fletcher WA, Biomaterials, 14, 26 (1993)
Schwartz M, Guterman H, Kost J, Biomaterials, 41, 65 (1998)
Hoshi T, Saiki H, Kuwazawa S, Tsuchlya C, Chen Q, Anzai JI, Anal. Chem., 73, 5310 (2001)
Nohara S, Wada H, Furukawa N, Inoue H, Morita M, Iwakura C, Electrochim. Acta, 48(6), 749 (2003)
Huang R, Hu N, Biophys. Chem., 104, 199 (2003)
Oxley HR, Corkhill PH, Fitton JH, Tighe BJ, Biomaterials, 14, 1064 (1993)
Zheng H, Xue H, Zhang Y, Shen Z, Biosens. Bioelectron., 17, 541 (2002)
Hassan CM, Doyle FJ, Peppas NA, Macromolecules, 30(20), 6166 (1997)
Sieg A, Guy RH, Charro MBD, Pharm. Sci., 92, 2295 (2003)
Tierney M, Tamada J, Potts R, Jovanovic L, Garg S, Biosens. Bioelectron., 16, 621 (2001)
Tamada J, Bohannon N, Potts R, Nat. Med., 1, 1198 (1995)
Haldon RA, Lee BE, Br. Polym. J., 4, 491 (1972)
KMH Co. Ltd., Kor. Pat. 10-0453483 (2007)
KMH Co. Ltd., Kor. Pat. 10-0832242 (2008)

[Referenced By]

[1] Choi JH, Park BH, Han YA, Kim SJ, Lim JO, Polym.(Korea), 28(1), 86 (2004)

[2] Kwon SK, Polym.(Korea), 18(6), 1055 (1994)

[3] Kurnik RT, Berner B, Tamada J, Potts RO, J. Electrochem. Soc., 145(12), 4119 (1998)

[4] Jung DY, Magda JJ, Han IS, Macromolecules, 33(9), 3332 (2000)

[5] Park YM, Kim US, Sung YK, Polym.(Korea), 15(3), 356 (1991)

[6] Tierney M, Tamada J, Potts R, Biosens. Bioelectron., 16, 621 (2001)

[7] Miyata T, Uragami T, Nakamae K, Adv. Drug Deliver. Rev., 54, 79 (2002)

[8] Seidel JM, Malmoge SM, Material Research, 3, 79 (2000)

[9] Garrett Q, Laycock B, Garrett R, Invest. Ophth. Vis. Sci., 41, 1687 (2000)

[10] Sack R, Jones B, Antignani A, Libow R, Harvey H, Invest. Ophth. Vis. Sci., 28, 842 (1987)

[11] Garrett Q, Chatelier R, Griesser H, Milthorpe B, Biomaterials, 19, 2175 (1998)

[12] Castillo E, Koenig J, Anderson J, Lo J, Biomaterials, 6, 338 (1985)

[13] Megan SL, Martina H, Stenzelb H, Simmonsa A, Milthorpea BK, Biomaterials, 27, 1341 (2006)

[14] Ito T, Hioki T, Yamaguchi T, Shinbo T, Nakao S, Kimura S, J. Am. Chem. Soc., 124(26), 7840 (2002)

[15] Traian VC, Constable IJ, Crawford GJ, Vijayasekaran S, Thompson DE, Chen YC, Fletcher WA, Biomaterials, 14, 26 (1993)

[16] Schwartz M, Guterman H, Kost J, Biomaterials, 41, 65 (1998)

[17] Hoshi T, Saiki H, Kuwazawa S, Tsuchlya C, Chen Q, Anzai JI, Anal. Chem., 73, 5310 (2001)

[18] Nohara S, Wada H, Furukawa N, Inoue H, Morita M, Iwakura C, Electrochim. Acta, 48(6), 749 (2003)

[19] Huang R, Hu N, Biophys. Chem., 104, 199 (2003)

[20] Oxley HR, Corkhill PH, Fitton JH, Tighe BJ, Biomaterials, 14, 1064 (1993)

[21] Zheng H, Xue H, Zhang Y, Shen Z, Biosens. Bioelectron., 17, 541 (2002)

[22] Hassan CM, Doyle FJ, Peppas NA, Macromolecules, 30(20), 6166 (1997)

[23] Sieg A, Guy RH, Charro MBD, Pharm. Sci., 92, 2295 (2003)

[24] Tierney M, Tamada J, Potts R, Jovanovic L, Garg S, Biosens. Bioelectron., 16, 621 (2001)

[25] Tamada J, Bohannon N, Potts R, Nat. Med., 1, 1198 (1995)

[26] Haldon RA, Lee BE, Br. Polym. J., 4, 491 (1972)

[27] KMH Co. Ltd., Kor. Pat. 10-0453483 (2007)

[28] KMH Co. Ltd., Kor. Pat. 10-0832242 (2008)