혈액대용물질의 제조 및 특성 평가

김기범; 박재관; 김성종; 김종수; 유일수; 김민호; 홍철운; 김진상; 강형섭; Gi-Beum Kim; Jai-Koan Park; Seong-Jong Kim; Jong-Soo Kim; Il-Soo You; Min-Ho Kim; Chul-Un Hong; Jin-Shang Kim; Hyung-Sub Kang

Korean Chemical Engineering Research, Vol.46, No.3, 626-632, June, 2008

Export Citation

혈액대용물질의 제조 및 특성 평가

Estimate of Characteristics and Manufacture of Blood Substitutes

김기범, 박재관¹, 김성종², 김종수², 유일수³, 김민호⁴, 홍철운⁵, 김진상, 강형섭^†

전북대학교 수의과대학 약리학교실, 561-756 전북 전주시 덕진구 덕진동1가 664-14
¹CIC, 565-854 전북 완주군 이서면 이문리 711
²전북대학교 공과대학 화학공학부, 561-756 전북 전주시 덕진구 덕진동1가 664-14
³전북대학교 공과대학 고분자나노공학과, 561-756 전북 전주시 덕진구 덕진동1가 664-14
⁴전북대학교 의학전문대학원 흉부외과학교실, 561-756 전북 전주시 덕진구 덕진동1가 664-14
⁵전북대학교 공과대학 바이오메디칼공학부, 561-756 전북 전주시 덕진구 덕진동1가 664-14

Gi-Beum Kim, Jai-Koan Park¹, Seong-Jong Kim², Jong-Soo Kim², Il-Soo You³, Min-Ho Kim⁴, Chul-Un Hong⁵, Jin-Shang Kim, and Hyung-Sub Kang^†

Department of Pharmacology, Collage of Veterinary Medicine, Chonbuk National University, 664-14, Duckjin-dong 1ga, Duckjin-gu, Jeonju, Jeonbuk 561-756, Korea
¹CIC, 711 Imun-ri Iseo-myeon, Wanju-gun, Jeollabuk-Do, 565-854, Korea
²Division of Chemical Engineering, College of Engineering, Chonbuk National University, 64-14, Duckjin-dong 1ga, Duckjin-gu, Jeonju, Jeonbuk 561-756, Korea
³Department of Polymer Nano Science & Technology, College of Engineering, Chonbuk National University, 64-14, Duckjin-dong 1ga, Duckjin-gu, Jeonju, Jeonbuk 561-756, Korea
⁴Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical Schools, 664-14, Duckjin-dong 1ga, Duckjin-gu, Jeonju, Jeonbuk 561-756, Korea
⁵Division of Biomedical Engineering, College of Engineering, Chonbuk National University, 664-14, Duckjin-dong 1ga, Duckjin-gu, Jeonju, Jeonbuk 561-756, Korea

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초록

본 연구는 헤모글로빈을 계란의 인지질로 microencapsulation한 hemosome과 PFC 유화액을 제조하여 산소전달 특성을 향상시키고자 하였다. 실험결과 fluosol-DA를 sonication하여 평균입자크기가 437 nm의 안정성 있는 유화액을 제조할 수 있었으며, glycerol의 농도를 증가시킴으로써 유화시간을 줄이고 안정도를 높일 수 있었다. 소 혈액으로부터 추출한 헤모글로빈을 달걀노른자로부터 추출한 인지질로 microencapsulation하여 직경 0.8 μm의 hemosome을 얻을 수 있었다. Hemosome의 산소포화도 곡선은 정상혈액의 적혈구와 같이 S자형을 보였으며 P50은 24 mmHg이었다. Hemosome과 혈액을 1:4(V/V%)의 혼합한 혼합용액에서의 산소 포화도는 정상혈액과 유사한 결과를 보였으며, PFC 유화액과 혈액을 1:4(V/V%)로 혼합한 혼합용액에도 정상혈액과 유사한 결과를 보였다.

The purpose of this study was to enhance gas exchange by producing hemosome, a hemoglobin microencapsulated with phospholipid of egg, and perfluorocarbone(PFC) emulsion solution. In the experiment, stable emulsion solution with 437 nm of mean particle size could be produced by Flusol-DA sonication, and shortening of emulsion time could be attained with higher stability as well. 0.8 μm sized hemosome could be produced by microencapsulation of hemoglobin with phospholipid extracted from egg yolk. The pattern of oxygen saturation curve of hemosome was S shape, which is similar to that found in normal blood, and P50 was measured to be 24 mmHg. The oxygen saturation in the mixed solution of hemosome and blood in 1:4(V/V%) ratio was similar to that of normal blood, and the same result was found in the mixed solution of PFC emulsion and blood in 1:4(V/V%) ratio.

Keywords:Blood Substitutes;Perfluorocarbone Emulsion;Microencapsulate Hemoglobin;Hemosome;Oxygen Dissociation

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[1] Vaslef SN, Cook KE, Leonard RJ, Mockros LF, Anderson RW, ASAIO J., 40, M522 (1994)

[2] Baskaran H, Ph.D. Dissertation, The Pennsylvania State University (1997)

[3] Federspiel WJ, Lund LW, Bultman JA, Wanant S, Matoney J, Golob JF, Frankowski BJ, Watach M, Litwak P, Hattler BG, ASAIO J., 45, 127 (1999)

[4] Kim GB, Kwon TK, Lee SC, Kim SJ, Cheong IS, Oh IH, Kim KJ, Byun YS, Jheong GR, Korean Chem. Eng. Res., 42(2), 151 (2004)

[5] Kim GB, Kim SJ, Hong CU, Kwon TK, Kim NG, Korean J. Chem. Eng., 22(4), 521 (2005)

[6] Kim GB, Hong CU, Kwon TK, J. Artif. Organs, 9, 34 (2006)

[7] Kim GB, Hong CU, Kwon TK, Jpn. J. Appl. Phys., 45(4B), 3811 (2006)

[8] Winslow RM, The Johns Hopkins University Press, Baltimore, USA (1992)

[9] Alpha Therpeutic Corporation. Fluosol 20% intravascular perflorochemical emulsion delivers oxygen to protect the heart during PTCA. Product Monograph, Alpha Therapeutic Corp., Los Angeles (1990)

[10] Ivanitsky GR, Vorobyev SI, Product Monograph; Perftoran Co., Pushchino, Russia (1997)

[11] Park JK, Ph.D. Dissertation, Chonbuk National University (2003)

[12] Szebeni J, Di Iorio EE, Hauser H, Winterhalter KH, Biochemistry, 24, 2827 (1985)

[13] Szoka F, Papahadjopoulos D, Proc. Natl. Acad. Sci., 75, 4194 (1978)

[14] Fujita T, Sumaya T, Yokohama K, Europ. Surg. Res., 3, 436 (1971)