POSITIVE CHARGE WATER SOLUBLE PRODRUG OF ARYL- AND HETEROARYL-PROPIONIC ACID HAVING VERY FAST SKIN PERMEABILITY

摘要

PROBLEM TO BE SOLVED: To avoid side effects of NSAIA by enhancing solubility of NSAIA in gastric juices, and enhancing its permeability through membranes and skin barriers, which may make it applicable for transdermal administration (topical application).SOLUTION: Novel positive charge water soluble prodrugs of aryl- or heteroaryl-propionic acid represented by formula (1) and formula (2) are synthesized. The prodrugs are distributed through human skin 100 to 130 times faster than parent drugs thereof. The prodrugs reach a peak plasma level in only about 40 to 50 minutes when the prodrugs are administrated transdermally. The prodrugs are used pharmaceutically with not only oral administration, but also transdermal administration for a treatment of NSAIA-remediable situation in human or animals and can avoid most of side effects of NSAIA.