胆盐/磷脂混合胶束对疏水性天然药物增溶性能的研究

Effects of Bile Salt-Phosphatidylcholine-Mixed Micelles on the Solubility of Natural Product Hydrophobic Drugs

目的:研究胆盐/磷脂混合胶束(BS/PC-MM)体系对疏水性天然药物的增溶能力及影响因素。方法:选择不同纯度的大豆磷脂(SPC)、蛋黄磷脂(EPC)与高纯度的胆酸盐制备胆盐/磷脂混合胶束(BS/PC-MM)。以透光率方法测定胆酸盐对磷脂的溶解能力,以20(S)人参皂苷Rg3、Rh2、黄芪甲苷、20(S)原人参二醇、原人参三醇和呋喃二烯为疏水性模型药物,考察了SDC/SPC-MM对药物的增溶特性。结果:高纯度的大豆磷脂和蛋黄磷脂适合制备成澄明的BS/PC-MM溶液。胆酸盐对磷脂的增溶能力为,脱氧胆酸钠>胆酸钠,胆酸盐对蛋黄磷脂的溶解度增加略高于大豆磷脂。20(S)原人参二醇、原人参三醇和呋喃二烯与SPC的亲和性较高。而20(S)人参皂苷Rh2、Rg3和黄芪甲苷与SDC的亲和性强,SDC/SPC-MM的脂质总质量增加,疏水性药物的溶解度提高。结论:胆盐/磷脂混合胶束(BS/PC-MM)对疏水性药物具有较好的溶解度,增溶能力受药物的理化性质和混合胶束的组成影响,可成为疏水性药物的非肠道给药新型载体。

Objective： To research the effects of bile Salt Phosphatidylcholine-Mixed Micelles （BS/PC-MM） on the solubility of hy natural product drophobic drugs and relevant factors. Methods： To select soya phosphatidylcholine and egg yolk phosphatidylcho- line with different purities by bile sale prepared BS/PC-MM. The maximum amount of PC that can be solubilized by BS was deter- mined by measuring the light transmission at 660 nrn in the prepared MM. Ginsenosides 20 （S）-Rg3, Rhz, Astragaloside IV, 20 （S）-protopanaxadiol, 20（S）-protopanaxatriol and Furanodiene were studied to dissolve characteristic in SDC/SPC-MM. Results： Only highly pure grades of SPC and EPC are suitable for the preparation of clear solution of BS/PC-MM. The average size 11. 3nm, cumulate size 32. 3nm, zeta potential--26.91my, in SDC/SPC-MM. The solubilizing capacity of different BS towards PC in- creased in the following order： sodium deoxycholate （SDC）~Sodium cholate （SC）. Moreover, egg phosphatidylcholine（EPC） was solubilized to a higher extent than SPC. Ginsenosides 20（S）-Rg3., Rhz and Astragaloside IV displayed higher affinity for MM com- pared with BS alone, whereas 20（S）-protopanaxadiol, 20（S）-protopanaxatriol and Furanodiene displayed relatively higher affinity for BS alone. The linear increase in the solubility of hydrophobic drugs were with an increase in concentration of MM. Conclusion： The solubility study of hydrophobic drugs in the prepare MM showed substantial enhancement of solubility. The extent of solubili- ty is essentially affected by .the chemical nature of the drug and the composition of MM. BS/PC-MM can be used as a parenteral new carrier for poorly water-soluble drugs.