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In Vitro and In Vivo Studies of Topical Delivery System of Gentisic Acid in Hairless Mice
Bian, ShengJie,Zheng, JunMin,Kim, Jung-Sun,Choi, Myeong Jun,Chung, Ho-Kwon,Lee, Chi-Ho,Kim, Dae-Duk 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3
Gentisic acid is a skin-whitening agent which inhibits the tyrosinase activity, an essential enzyme in the process of biological synthesis of melanin. Since melanin is synthesized in melanocytes located between the viable epidermis and dermis layer, drug amount delivered into the epidermis/dermis layer can provide valuable information for the biological effect of skin-whitening agents. The purpose of this study was to prepare the gentisic acid patches with 2% dodecylamine as enhancer, and to observe the in vitro skin permeation and in vivo skin deposition of gentisic acid. Gentisic acid in Duro-Tak 87-2510 patch formulation permeated across hairless mouse skin at the rate of 40.79㎍/㎠/hr. In vivo study showed that the gentisic acid amount in both the stratum corneum and the viable epidermis/dermis increased with the increase of application time. The amount of gentisic acid in the stratum corneum was higher than that in the epidermis/dermis layer, and was expected to provide a reservoir effect even after removing the patches. Thus, the patch formulation seems to be useful for the topical delivery of ski-whitening agent into the epidermis/dermis layer, the target site.
Lee, Dong Kun,Bian, Shengjie,Rahman, Md. Aminur,Shim, Yoon-Bo,Shim, Insop,Choe, Eun Sang Elsevier 2008 european journal of pharmacology Vol.590 No.1
<P><B>Abstract</B></P><P>This study was conducted to determine the phosphorylation state of <I>N</I>-methyl-<SMALL>D</SMALL>-aspartate (NMDA) NR1 subunit on serine residues 896 (Ser896) and 897 (Ser897), the extracellular signal-regulated kinase 1/2 (ERK1/2), and the cyclic AMP response element-binding protein (CREB) after repeated exposure to cocaine (20?mg/kg, once daily for 9?days) in the dorsal striatum of rats. The real-time changes of glutamate concentration evoked by repeated cocaine injections were examined using a glutamate biosensor in order to evaluate the correlation between glutamate concentration and the change in these phosphoproteins. The results of this study showed that the immunoreactivity of phosphorylated (p)NMDA NR1 subunit at Ser896 and Ser897 as well as pERK1/2, but not pCREB, in the dorsal striatum was increased at 30?min and then returned to basal levels 4?h after repeated cocaine injections. Similarly, glutamate responses evoked by repeated cocaine injections were also increased 30?min after repeated cocaine injections for 3?days and were prolonged by the 9th day of treatment. However, the glutamate responses were not detected at 4?h after repeated cocaine injections for 5?days. In addition, the elevated immunoreactivity of the phosphoproteins 2?h after repeated cocaine injections was attenuated by the blockade of dopamine D1 receptors and NMDA receptors with the SCH23390 or MK801 antagonists, respectively. These findings suggest that glutamate release and dopamine D1 and NMDA receptor stimulation after repeated exposure to cocaine are associated with NMDA NR1 subunit, ERK1/2 and CREB phosphorylation in the dorsal striatum.</P>