| 摘要 |
<p>The novel positively charged pro-drugs of beta-lactam antibiotics in the general 'Structure 4' were designed. The positively charged amino group of the pro-drug not only makes the drugs soluble in water, but also bonds to the negative charge on the phosphate head group of membranes. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the prodrug. When the molecules of membrane move, the membrane may 'crack' a little bit due to the bonding of the prodrug. This will let the prodrug insert into the membrane. At pH 7.4, only about 99% of amino group is protonated. When the amino group is not protonated, the bonding between the amino group of the prodrug and the phosphate head group of membrane will disassociate, and the prodrug will enter the membrane completely. When the amino group of the prodrug flips to the other side of the membrane and thus become protonated, then the prodrug is pulled into the cytosol, a semiliquid concentrated aqueous solution or suspension. The results suggest that the pro-drugs diffuses through human skin, blood-brain, and blood-milk barriers hundreds times faster than do beta-lactam antibiotics. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating beta-lactam antibiotics-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments. Controlled transdermal administration systems of the prodrug enables beta-lactam antibiotics to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of beta-lactam antibiotics. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children or animals, will be much easier.</p> |
