5-氨基酮戊酸磷脂复合物的研究

 目的提高光动力治疗药物5-氨基酮戊酸(ALA)的脂溶性从而增强其透皮吸收效果。方法制备ALA的磷脂(PC)复合物(ALA-PC);差示量热扫描法(DSC)研究其热力学性质;通过测定油水分配系数P_OCT/PBS、体外渗透试验和小鼠经皮给药试验,比较ALA和ALA-PC的透皮效果。结果ALA与PC的复合率为99.6%;DSC图谱表明ALA-PC是不同于ALA、PC、ALA与PC的物理混合物(ALA+PC)的新物相;ALA-PC的油水分配系数为ALA的7.8倍;与ALA相比,ALA-PC的表观渗透系数显著增加且在正常小鼠皮肤内诱导产生的原卟啉IX(PpIX)的量和透过深度均提高。结论ALA-PC可提高ALA的脂溶性和透皮效果,有望成为透皮给药进行光动力治疗的有效药物。

Studies on the Compounds of 5-Aminolevulinic Acid and Phospholipid

OBJECTIVE To increase the transdermal ratio of ALA through its phospholipid compound(ALA-PC) which possesses enhanced lipophilicity.METHODS ALA-PC was prepared.The thermodynamics properties of ALA-PC were studied by DSC.Oil-water partition coefficient(P_(O/W)),in vitro permeation and in vivo transdermal experiments were conducted to study the lipophilicity and transdermal properties of ALA-PC.RESULTS A compound ratio of 99.6% was obtained.Some new peaks appeared in the DSC spectra of ALA-PC,as compared with ALA,PC and ALA PC.The P_(O/W) of ALA-PC was 7.8 times as that of ALA,while in vitro apparent permeability coefficient of ALA-PC increased significantly.More PpIX was induced by ALA-PC in normal mice skin,which existed in the deeper area.CONCLUSION ALA-PC was confirmed to be a new substance.The transdermal ability of ALA was improved after being complexed with PC.The results suggested that ALA-PC would be a promising transdermal delivery drug for photodynamic therapy.