Synthesis Of D-Glucosamine Amide And Their Effects On Baicalin Transdermal Delivery Properties

Transdermal drug delivery system (TDDS) attracts the attention from the pharmaceutical industry. However, skin barrier limits the development of TDDS. Effective transdermal enhancers overcome this problem. The purpose of this dissertation is to develop a kind of safe, effective transdermal enhancers, further to advance TDDS.The amine in D-glucosamine was first protected by benzaldehyde,then the hydroxy groups were acetylated,finally the elimination of Schiff base was performed to get important intermediate—1,3,4,6-tetra-O-acetyl-2-deoxy-2-amine-β-D-glucopy- ranose hydrochloride salt(DGAcHCl). Then DGAcHCl was reacted with long chain fatty acid or ferulic acid in the present of DCC as dehydrating agent. At last, etherification and ester exchange was done and two series of D-glucosamine amide were synthesized. The structures were confirmed by IR, 1H NMR and FAB-MS.In this dissertation, Baicalin was employed as the model medicine to investigate the effect of D-glucosamine amide on the drug skin permeation properties. Meanwhile, Azone and OA were used as control. Results indicated that all D-glucosamine amide exhibit higher transdermal enhancement effects than OA. Among the compounds, DGS, DGP, DGD, DGC, DGH, DGO and DGFAP showed higher enhancement effects than Azone. Permeation properties of the D-glucosamine amide were studied relating to the chemical structure, including the length of alkyl chain, polar group and the double bond. In the series of 2-deoxy-2-alkylamide-β-D-glucopyranose, the alkyl chain containing 8 carbon atoms performed the highest enhancing factor. However, the alkyl chain containing 16 carbon atoms was observed to result in the best effect in the series of 2-deoxy-2-(4′-alkoxy-3′-methoxy cinnamoylamide)-β-D-glucopyranose. When the length of alkyl chain remains the same, the molecules having glucopyranose as the polar group led to better permeation effect. In the end, when other factors remain the same, the compound containing double bond in the alkyl chain showed better permeation enhancing factor.