| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | Solubilized bile acid-heparin conjugate for oral delivery of heparin |
| 초록 | The delivery of hydrophilic macromolecule via oral route is highly difficult, because of it’s low diffusivity and partition coefficient. Therefore, to control its size and hydrophobcity is needed for enhancing the permeability of macromolecular drugs in intestinal membrane. Therefore, LMWH- DOCA was developed by conjugation with deoxycholic acid as a strategy for increasing the hydrophobicity of LMWH1, which is macromolecular anticoagulant drug. However, LMWH-DOCA conjugate itself did not show a significant absorption in the GI tract. We believe that this may be mainly due to reduced solubility caused by the self-aggregation of amphiphilic LMWH-DOCA conjugate in aqueous condition. In our study, we used the combination methods with above DOCA-conjugating system and solubilzer system using DMSO solution and thereby enhancing the oral bioavailability of LMWH-DOCA in mice. Also, for the clinical application, we observed its absorption in non-human primates after oral administration. For the preperation of orally active heparin, Fraxiparin, which is a low molecular weight heparin, was conjugated with deoxycholic acid. The absorption of LMWH-DOCA after its oral administration was measured by FXa assay according to the conjugation ratio of DOCA, concentration of DMSO solution and dose of LMWH-DOCA, respectively. As expected, the LMWH-DOCA conjugates dissolved in the aqueous DMSO formulation when administered orally to mice and monkeys produced a remarkable improvement in the bioavailability of LMWH-DOCA. From these results, we found that LMWH-DOCA conjugates completely dissolved in 10% DMSO solution and showed high absorption in the intestine of monkeys (16.6% bioavailability) as well as in mice (17.6% bioavailability) without causing any damage in intestinal tissues. 참고문헌 1. S. K. kim, and Y. Byun, thrombosis research, (2005) |
| 저자 | 김상균, 변영로 |
| 소속 | 서울대약학대 |
| 키워드 | bile acid; LMWH; oral; conjugate; monkey |
