| 摘要 |
The novel positively charged pro-drugs of ibuprofen in the general formul a (I) "Structure 1" were designed and synthesized. The compounds of the gene ral formula (I) "Structure 1" indicated above can be prepared from functiona l derivatives of ibuprofen, (for example acid halides or mixed anhydrides), by reaction with suitable alcohols, thiols, or amines. The positively charge d amino groups of these pro-drugs not only largely increases the solubility of the drugs, but also bonds to the negative charge on the phosphate head gr oup of membranes and pushes the pro-drug into the cytosol. The experiment re sults suggest that the pro-drug, diethylaminoethyl 2-(p-isobutylphenyl) prop ionate.AcOH, diffuses through human skin -250 times faster than ibuprofen it self and -125 times faster than ethyl 2-(p-isobutylphenyl) propionate. In pl asma, more than 90% of these pro-drugs can change back to the drug in a few minutes. The prodrugs can be used medicinally in treating any ibuprofen-trea table conditions in humans or animals and be administered not only orally, b ut also transdermally for any kind of medical treatments and avoid most of t he side effects of ibuprofen, most notably GI disturbances such as dyspepsia , gastroduodenal bleeding, gastric ulcerations, and gastritis. Controlled tr ansdermal administration systems of the prodrugenables the ibuprofen to reac h constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of ibuprofen.
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