POSITIVELY CHARGED WATER-SOLUBLE PRODRUG HAVING VERY HIGH SKIN PENETRATION RATE FOR ACETAMINOPHEN AND RELATED COMPOUND

摘要

PROBLEM TO BE SOLVED: To overcome adverse effects relating to the use of acetaminophen and related compounds.SOLUTION: Novel positively charged prodrugs shown in Fig.4 for acetaminophen, acetaminosalol and related compounds are designed and synthesized. Positively charged amino groups of the prodrugs not only greatly increase solubility of a drug but also connect with negative charges on phosphate head groups of a membrane to push the prodrug into cytosol. The prodrugs diffuse about ≤150 times as fast as acetaminophen, acetaminosalol and the related compounds through human skin. The prodrugs are used for the treatment of the conditions for which NSAIA treatment is possible in human or animal pharmaceutically by not only the oral administration but also dermal administration, and can evade most side effects of NSAIA.