Shibayama H, Hisama M, Matsuda S, Ohtsuki M
Department of Dermatology, Jichi Medical University, Shimotsuke, Japan.
Skin Pharmacol Physiol. 2008;21(4):235-43. doi: 10.1159/000139128. Epub 2008 Jun 14.
A novel amphiphilic vitamin C (VC) derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), which possesses a C(18) alkyl chain attached to a stable ascorbate derivative, sodium L-ascorbic acid 2-phosphate (VCP-Na), was evaluated as a topical prodrug of VC with transdermal activity in human living skin equivalent (LSE) models. The permeation assay used was EPI-606X in the Franz-type diffusion cell system. VCP-IS-2Na exhibited much better permeability than VC and VCP-Na. The accumulation assays applied were EPI-200X and LSE-high by the dynamic system. The increased skin accumulation of VCP-IS-2Na was superior to that of VCP-Na and VC. VCP-IS-2Na that is susceptible to enzymatic hydrolysis by esterase and/or phosphatase released VC in the skin. Measurement of the metabolites that permeated and accumulated from the skin model suggested that VCP-IS-2Na was mainly metabolized via VCP-Na to VC in EPI-606X and EPI-200X, while it was mainly metabolized directly to VC in TESTSKIN LSE-high. Thus, these characteristics indicate that the novel VC derivative, VCP-IS-2Na, may be advantageous as a readily available source of VC for skin care applications.
一种新型两亲性维生素C（VC）衍生物，异硬脂酰2-O-L-抗坏血酸磷酸二钠（VCP-IS-2Na），其具有连接到稳定抗坏血酸衍生物L-抗坏血酸2-磷酸钠（VCP-Na）的C(18)烷基链，在人类活皮肤等效物（LSE）模型中被评估为具有透皮活性的VC局部前药。所使用的渗透测定法是在Franz型扩散池系统中进行的EPI-606X测定法。VCP-IS-2Na表现出比VC和VCP-Na更好的渗透性。所应用的蓄积测定法是通过动态系统进行的EPI-200X和LSE-high测定法。VCP-IS-2Na在皮肤中的蓄积增加优于VCP-Na和VC。易被酯酶和/或磷酸酶酶促水解的VCP-IS-2Na在皮肤中释放出VC。对从皮肤模型渗透和蓄积的代谢物的测量表明，在EPI-606X和EPI-200X中，VCP-IS-2Na主要通过VCP-Na代谢为VC，而在TESTSKIN LSE-high中，它主要直接代谢为VC。因此，这些特性表明，新型VC衍生物VCP-IS-2Na作为皮肤护理应用中易于获得的VC来源可能具有优势。
