| 摘要 |
The novel positively charged pro-drugs of beta-lactam antibiotics in the general 'Structure 4' were designed. The positively charged amino group of t he 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 m ay '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 t he amino group of the prodrug and the phosphate head group of membrane will disassociate, and the prodrug will enter the membrane completely. When the a mino group of the prodrug flips to the other side of the membrane and thus b ecome protonated, then the prodrug is pulled into the cytosol, a semi-liquid concentrated aqueous solution or suspension. The results suggest that the p ro-drugs diffuses through human skin, blood-brain, and blood-milk barriers h undreds times faster than do beta-lactam antibiotics. In plasma, more than 9 0% 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-tre atable conditions in humans or animals. The prodrugs can be administered tra nsdermally for any kind of medical treatments. Controlled transdermal admini stration systems of the prodrug enables beta-lactam antibiotics to reach con stantly optimal therapeutic blood levels to increase effectiveness and reduc e the side effects of beta-lactam antibiotics. Another great benefit of tran sdermal administration of these pro-drugs is that administering medication, especially to children or animals, will be much easier.
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