| 摘要 |
Novel positively-charged prodrugs in a general formula (1) 'structure 1' of acetylsalicylic acid and acetylsalicylic acid analogues are designed and synthesized. The compounds of the general formula (1) 'structure 1' can be prepared by reacting functional derivatives (for example acid halides or mixed anhydrides) of acetylsalicylic acid or acetylsalicylic acid analogues with suitable alcohols, thiols or amines. The positively-charged amino groups of the pro-drugs not only substantially increase the solubility of the drugs, but also bond to negative charges at the phosphate terminal of biological membranes and push prodrug molecules into the cellular fluid. Experiment results suggest that the prodrug diethylaminoethyl acetylsalicylate-acetate has a human skin penetration speed faster than that of acetylsalicylic acid by nearly 400 times, and faster than that of ethyl acetylsalicylate by nearly 100 times. In plasma, 80% of the prodrug can change back to the drug in a few minutes. The prodrugs can be used medicinally in treating any aspirin-treatable diseases of human or animals and be administered not only orally, but also transdermally for any kind of medical treatments and avoid most of the side effects of acetylsalicylic acid and acetylsalicylic acid analogues, most notably side effects such as dyspepsia, gastroduodenal bleeding, gastric ulcerations and gastritis. A controlled transdermal administration systems of the prodrug enables acetylsalicylic acid and acetylsalicylic acid analogues in the blood to reach constantly optimal therapeutic blood levels to increase curative effect and reduce the side effects of acetylsalicylic acid. |
