Studies on Synthesis of Block Copolymers Containing Polyester and Polypeptide for Drug Delivery System Ⅰ. Synthesis and Characterization of Copolymer of L-Lactic Acid and L-Glutamic Acid

폴리펩티드-의약 전달체 및 폴리펩티드 공중합체의 합성 및 물성에 관한 연구 (Ⅰ) L-Lactic Acid 와 L-Glutamic Acid 공중합체의 합성 및 그의 물성

  • 김홍범 (동국대학교 화학과) ;
  • 성용길 (동국대학교 이과대학 화학과) ;
  • 정재희 (동국대학교 화학과) ;
  • 백형게 (동국대학교 화학과) ;
  • 민태진 (동국대학교 이과대학 화학과) ;
  • 김영순 (동국대학교 이과대학 화학과)
  • Published : 19900300

Abstract

As a possible biocompatible and biodegrable polymer skeleton for drug delivery system, block copolymers of L-lactic acid and L-glutamic acid with different composition were synthesized and characterized. Poly (L-lactide) was prepared by polymerization of L-lactide with zine oxide at $130^{\circ}C$ for 72 hrs. 3-Amino-l-propanol was introduced to poly (L-lactide) by an ester linkage in order to initiate polymerization. Polymerization of $\gamma-benzyl-L-glutamate-N-carboxyanhydride(\gamma-BLG-NCA)$ utiliizing the amino group of modified poly (L-lactide) as an initiator gave rise to the block copoly $(L-lactide-\gamma-benzyl-L-glutamate).$ The NMR study of resulting block copolymers showed that the composition of L-lactic acid and $\gamma-benzyl-L-glutamate$ in block copolymers was depended on the weight ratio of poly (L-lactide) and $\gamma-BLG-NCA.$ The thermal properties of the resulting block copolymers were determined by the differential scanning calorimetry and by the thermogravimetry.

의약 전달체에 사용되는 생체분해성 고분자로서 L-lactic acid 와 L-glutamic acid가 각기 다른 조성비로 이루어진 공중합체를 합성하였다. Poly (L-lactide)는 zink oxide를 이용하여 합성하였으며, Poly (L-lactide) 말단에 3-Amino-l-propanol을 도입시킨 다음 이미 합성된 γ-benzyl-L-glutamate-N-carboxyanhydride (γ-BLG-NCA)를 개환중합시켜서 block copoly (L-lactide-γ-benzyl-L-glutamate)를 합성하였다. NMR로써 L-lactide와 γ-BLG-NCA가 서로 일정한 비율로 이루어진 공중합체가 합성되었음을 확인하였으며, 생성된 공중합체들의 열적성질은 시차주사열량계법 및 열무게 측정법으로 조사하였다.

Keywords

References

  1. Polymer Science and Technology v.8 Polymers in Medicine and Surgery R. L. Kronenthal;R. L. Lronethal(ed.);Z. Oser(ed. );E. Martin(ed.)
  2. U. S. Patent. 4,470,297 assignors to Ethicon A. Kafrawy;F. V. Mattei;S. W. Shalaby
  3. Drug Design v.10 S. W. Kim;R. V. Pertersen;J. Feijen;E. J. Ariens(Ed.)
  4. Polymer v.20 D. K. Gilding;A. M. Reed
  5. Biopolymers v.15 W. D. Faller;M. S. Verlander;M. Goodman
  6. J. Polym. Sci. Macromol. v.12 R. W. Woody
  7. J. Med. Chem. v.7 Y. Kato;N. Umemoto;Y. Kayama;H. Fukushima;Y. Takeda;T. Hara;Y. Tsukada
  8. Yeon Ku Non jip v.17 J. Y. Kim;Y. J. Kim;Y. K. Sung
  9. Polymer (Korea) v.12 no.5 S. W. Jang;J. H. Kim;K. Y. Kim;Y. K. Sung;C. S. Cho
  10. Fed. Regist. v.40 no.121 Anon.(FDA)
  11. AD Report No. 748 U. S. Natl. Tech. Intorm. Seru. R. G. Sinclair;Gynn
  12. Biopolymeric Controlled Release System v.1 D. L. Wise;D. L. Wise(Ed.)
  13. Bull. Chem. Soc. Jap. v.38 T. Ozawa
  14. Anal. Chem. v.21 H. E. Kissinger
  15. J. Polym. Sci. v.6 E. S. Freedman;B. Carroll
  16. Thermal Methods and Analysis W. W. Wendlant
  17. Polym. J. v.19 K. Kugo;A. Ohji;T. Uno;J. Nishino
  18. Tetrahedron Lett. v.31 M. Mutter
  19. Makromolecules v.17 R. Kricheldorf;T. Mang;J. M. Jonte
  20. J. Polym. Sci. Polym. Chem. v.17 A. Schindler;D. Happer
  21. Mackromol. Chem. Suppl. v.12 H. R. Kricheldorf;J. M. Jonte;M. Berl
  22. Eur. Polym. J. v.19 F. E. Kohn;J. G. Van Ommen;J. Feifen
  23. Eur. Polym. J. v.10 S. Fririch;D. Gerther;A. Zlikha
  24. Ind. J. Chem. v.8 Mhala;J. P. Mishra
  25. J. Polym. Sci. Polym. Let. v.5 M. Goodman;M. D. Alagni
  26. Polymer v.23 B. Eling;S. Gogolewski;A. J. Penning