혈액대용물질의 제조 및 특성 평가

Estimate of Characteristics and Manufacture of Blood Substitutes

  • 김기범 (전북대학교 수의과대학 약리학교실) ;
  • 박재관 ;
  • 김성종 (전북대학교 공과대학 화학공학부) ;
  • 김종수 (전북대학교 공과대학 화학공학부) ;
  • 유일수 (전북대학교 공과대학 고분자나노공학과) ;
  • 김민호 (전북대학교 의학전문대학원 흉부외과학교실) ;
  • 홍철운 (전북대학교 공과대학 바이오메디칼공학부) ;
  • 김진상 (전북대학교 수의과대학 약리학교실) ;
  • 강형섭 (전북대학교 수의과대학 약리학교실)
  • Kim, Gi-Beum (Department of Pharmacology, Collage of Veterinary Medicine, Chonbuk National University) ;
  • Park, Jai-Koan (CIC) ;
  • Kim, Seong-Jong (Division of Chemical Engineering, College of Engineering, Chonbuk National University) ;
  • Kim, Jong-Soo (Division of Chemical Engineering, College of Engineering, Chonbuk National University) ;
  • You, Il-Soo (Department of Polymer Nano Science & Technology, College of Engineering, Chonbuk National University) ;
  • Kim, Min-Ho (Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical Schools) ;
  • Hong, Chul-Un (Division of Biomedical Engineering, College of Engineering, Chonbuk National University) ;
  • Kim, Jin-Shang (Department of Pharmacology, Collage of Veterinary Medicine, Chonbuk National University) ;
  • Kang, Hyung-Sub (Department of Pharmacology, Collage of Veterinary Medicine, Chonbuk National University)
  • 투고 : 2008.01.24
  • 심사 : 2008.03.10
  • 발행 : 2008.06.30

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 $0.8{\mu}m$의 hemosome을 얻을 수 있었다. Hemosome의 산소포화도 곡선은 정상혈액의 적혈구와 같이 S자형을 보였으며 $P_{50}$은 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. $0.8{\mu}m$ 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 $P_{50}$ 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.

키워드

과제정보

연구 과제 주관 기관 : 한국학술진흥재단

참고문헌

  1. Vaslef, S. N., Cook, K. E., Leonard, R. J., Mockros, L. F. and Anderson, R. W., "Design and Evaluation of a New, Low Pressure Loss, Implantable Artificial Lung," ASAIO J., 40, M522-M526(1994) https://doi.org/10.1097/00002480-199407000-00055
  2. Baskaran, H., "Blind-Ended Hollow Fiber Prototypes of the Penn State Intravascular Lung," Ph.D. Dissertation, The Pennsylvania State University(1997)
  3. Federspiel, W. J., Lund, L. W., Bultman, J. A., Wanant, S., Matoney, J., Golob, J. F., Frankowski, B. J., Watach, M., Litwak, P. and Hattler, B. G., "Ex-vivo Testing of the Intravenous Membrane Oxygenator(IMO)," ASAIO J., 45, 127(1999)
  4. Kim, G. B., Kwon, T. K., Lee, S. C., Kim, S. J., Cheong, I. S., Oh, I. H., Kim, K. J., Byun, Y. S. and Jheong, G. R., "Characteristics of Oxygen Transfer in Intravascular Lung Assist Device by Vibrating," Korean Chem. Eng. Res., 42(2), 151-162(2004)
  5. Kim, G. B., Kim, S. J., Hong, C. U., Kwon, T. K. and Kim, N. G., "Enhancement of Oxygen Transfer in Hollow Fiber Membrane by the Vibration Method," Korean J. Chem. Eng., 22(4), 521-527 (2005) https://doi.org/10.1007/BF02706636
  6. Kim, G. B., Hong, C. U. and Kwon, T. K., "Design of An Intravenous Oxygenstor," J. Artif. Organs, 9, 34-41(2006) https://doi.org/10.1007/s10047-005-0312-1
  7. Kim, G. B., Hong, C. U. and Kwon, T. K., "Vibration Characteristics of Piezoelectric Lead Zirconate Titanate by Fluid Flow in Intravascular Oxygenator," Jpn. J. Appl. Phys., 45(4B), 3811-3817(2006) https://doi.org/10.1143/JJAP.45.3811
  8. Winslow, R. M., "Hemoglobin-Basec Red Cell Substitutes," 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, G. R. and Vorobyev, S. I., "Perftoran Blood Substitute with Gas-Transporting Function," Product Monograph; Perftoran Co., Pushchino, Russia(1997)
  11. Park, J. K., "Characteristics of Gas Transfer in Intravenous Lung Assist Device by using Blood Substitute," Ph.D. Dissertation, Chonbuk National University(2003)
  12. Szebeni, J., Di Iorio, E. E., Hauser, H. and Winterhalter, K. H., "Encapsulation of Hemoglobin in Phosphoipid Liposomes: Characterization and Stability", Biochemistry, 24, 2827-2832(1985) https://doi.org/10.1021/bi00333a003
  13. Szoka, F. and Papahadjopoulos, D., "Procedure for Preparation of Liposomes with Large Internal Aqueous Space and High Capture by Reverse-phase Evaporation," Proc. Natl. Acad. Sci., 75, 4194-4198(1978)
  14. Fujita T., Sumaya T. and Yokohama, K., "Fluorocarbon Emulsion as a Candidate for Artificial Blood: Correlation Between Particle Size of the Emulsion and Acute Toxicity," Europ. Surg. Res. 3, 436-453(1971) https://doi.org/10.1159/000127590