Simulated Moving Bed를 이용한 Bupivacaine의 키랄 분리 (2) 모사에 의한 최적 조건 결정

한순구; 여미순; 이중기; 박태진; 구윤모; 노경호; Soon Koo Han; Mi Soon Yeo; Joong Kee Lee; Tae-Jin Park; Yoon Mo Koo; Kyung Ho Row

HWAHAK KONGHAK, Vol.41, No.6, 728-735, December, 2003

Export Citation

Simulated Moving Bed를 이용한 Bupivacaine의 키랄 분리 (2) 모사에 의한 최적 조건 결정

Chiral Separation of Bupivacaine by Simulated Moving Bed (2) Determination of Optimum Condition by Simulation

한순구, 여미순, 이중기 ¹, 박태진 ¹, 구윤모 , 노경호 ^†

인하대학교 초정밀생물분리기술연구센터, 402-701 인천시 용현동 253
¹한국과학기술연구원 나노환경연구센터, 136-791 서울시 성북구 하월곡동 39-1

Soon Koo Han, Mi Soon Yeo, Joong Kee Lee¹, Tae-Jin Park¹, Yoon Mo Koo , and Kyung Ho Row^†

Center for Advanced Bioseparation Technology, Inha University, 253, Yonghyun-dong, Nam-gu, Incheon 402-751, Korea
¹Eco-Nano Research Center, Korea Institute of Science and Technology, 39-1, Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Korea

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초록

본 연구에서는 경부외 마취제로 사용되고 있는 S-bupivacaine을 SMB를 이용하여 R-bupivacaine으로부터 분리하였다. 단일칼럼을 이용한 실험을 통해서 비선형 흡착평형식과 실험식으로부터 물질전달계수를 얻었다. PIM을 이용하여 얻은 경쟁 Langmuir 흡착평형식에서의 매개변수 a는 R-bupibacaine은 6.20, S-bupivacaine은 8.79 매개변수 b는 각기 0.364, 0.922 ml/mg이었다. 이 매개변수들은 상용 모사기에 적용되어 두 키랄물질을 분리하기 위한 최적조업조건을 얻었고, 실험적으로 확인하기 위해서 Kromasil^® CHI-TBB로 충진된 1 X 10 cm 칼럼이 2-2-2-2 구성으로 된 SMB를 이용하여 결과적으로 racemic bupivacaine을 98%이상 고순도로 분리하였다.

In this work, S-bupivacaine with the pharmacological activity of epidural anaesthesia was separated from R-bupivacaine by SMB (simulated moving bed). Nonlinear isotherm was suggested from the single column experiment and the mass transfer coefficient was obtained from an empirical equation. The parameters of a in competitive Langmuir adsorption equation empirically determined by PIM (pulsed input method) for R and S-bupibacaine were 6.20, 8.79 respectively, while those of b were 0.364, 0.922 ml/mg, respectively. These equilibrium and kinetic parameters were used by a commercially available simulator to find the optimum operating condition for resolving the two racemic mixtures. It was experimentally confirmed that based on these experimental conditions, the separation of bupivacaine enantiomers was successfully performed with the purity of more than 98% by SMB composed of eight column (2-2-2-2, 1×10 cm) packed with Kromasil^® CHI-TBB.

Keywords:Chiral Separation;Simulation;Simulated Moving Bed;Bupivacaine

[References]

Bhushan R, Martens J, J. Pharm. Biomed. Anal., 8, 259 (1990)
Ahuja S, Chiral Separations by Chromatography, Oxford Univ. Press, New York (2000)
Medvedovici A, Sandra P, Toribio L, David F, J. Chromatogr. A, 785, 159 (1997)
Pais LS, Loureiro JM, Rodrigues AE, AIChE J., 44(3), 561 (1998)
Miler L, Orihuela C, Fronek R, Honda O, J. Chromatogr. A, 849, 309 (1999)
Yang HY, Shim MH, Chang HK, Jang MH, Lee TH, Kim YJ, Chung JH, Kim CJ, Neurosci. Lett., 344, 33 (2003)
Mio Y, Fukuda N, Kusakari Y, Tanifuji Y, Anesthesiology, 97, 1168 (2002)
Gu XQ, Fryirs B, Mater LE, J. Chromatogr. B, 719, 135 (1998)
Yoon JY, Lee JK, Suh SS, Choi MH, Park TJ, HWAHAK KONGHAK, 41(6), 736 (2003)
Slater MJ, The Principles of Ion Exchange Technology, Butterw-worth, Heinemann, Oxford (1991)
Storti G, Mazzotti M, Carra S, Morbidelli M, Chem. Eng. Sci., 44, 1329 (1989)
Mazzotti M, Storti G, Morbidelli M, AIChE J., 40(11), 1825 (1994)
Mazzotti M, Storti G, Morbidelli M, AIChE J., 42(10), 2784 (1996)
Guiochon G, Golshan-Shirazi S, Katti AM, Fundamentals of Preparative and Nonlinear Chromatography, Academic Press, Boston (1994)
Choi YS, Lee JW, Row KH, HWAHAK KONGHAK, 38(4), 474 (2000)
Wilke CR, Chang P, AIChE J., 1, 264 (1955)
Partington J, An Advanced Treatise on Physical Chemistry, Vol. I, Fundamental Principles: The Properties of Gases, Longmans, Green, New York (1949)
Grunberg L, Nissan AH, Nature, 164, 799 (1949)

[Referenced By]

[Related Articles]

[1] Bhushan R, Martens J, J. Pharm. Biomed. Anal., 8, 259 (1990)

[2] Ahuja S, Chiral Separations by Chromatography, Oxford Univ. Press, New York (2000)

[3] Medvedovici A, Sandra P, Toribio L, David F, J. Chromatogr. A, 785, 159 (1997)

[4] Pais LS, Loureiro JM, Rodrigues AE, AIChE J., 44(3), 561 (1998)

[5] Miler L, Orihuela C, Fronek R, Honda O, J. Chromatogr. A, 849, 309 (1999)

[6] Yang HY, Shim MH, Chang HK, Jang MH, Lee TH, Kim YJ, Chung JH, Kim CJ, Neurosci. Lett., 344, 33 (2003)

[7] Mio Y, Fukuda N, Kusakari Y, Tanifuji Y, Anesthesiology, 97, 1168 (2002)

[8] Gu XQ, Fryirs B, Mater LE, J. Chromatogr. B, 719, 135 (1998)

[9] Yoon JY, Lee JK, Suh SS, Choi MH, Park TJ, HWAHAK KONGHAK, 41(6), 736 (2003)

[10] Slater MJ, The Principles of Ion Exchange Technology, Butterw-worth, Heinemann, Oxford (1991)

[11] Storti G, Mazzotti M, Carra S, Morbidelli M, Chem. Eng. Sci., 44, 1329 (1989)

[12] Mazzotti M, Storti G, Morbidelli M, AIChE J., 40(11), 1825 (1994)

[13] Mazzotti M, Storti G, Morbidelli M, AIChE J., 42(10), 2784 (1996)

[14] Guiochon G, Golshan-Shirazi S, Katti AM, Fundamentals of Preparative and Nonlinear Chromatography, Academic Press, Boston (1994)

[15] Choi YS, Lee JW, Row KH, HWAHAK KONGHAK, 38(4), 474 (2000)

[16] Wilke CR, Chang P, AIChE J., 1, 264 (1955)

[17] Partington J, An Advanced Treatise on Physical Chemistry, Vol. I, Fundamental Principles: The Properties of Gases, Longmans, Green, New York (1949)

[18] Grunberg L, Nissan AH, Nature, 164, 799 (1949)