Numerous drugs are now known and currently in use that are not absorbed at all, or are absorbed only poorly, from the gastrointestinal tract. In particular, many important semisynthetic cephalosporin antibiotics that are now available and are routinely used must be administered parenterally. Cephalothin Sodium, for example, is administered intramuscularly or intravenously, thus requiring a trained medical person to treat the patient. It has long been an objective of research to provide potent drugs that are orally active, especially in the field of cephalosporin and penicillin antibiotics. Jansen and Russell prepared several acyloxymethyl esters of various penicillins and found that some of the esters were orally active; U.S. Pat. No. 3,250,679. At the same time, however, Jansen and Russell reported that of the many closely related acyloxymethyl esters which were prepared and tested, only the acetoxymethyl ester of benzylpenicillin displayed oral absorption to a significant extent. In fact, some acyloxymethyl esters of certain penicillins showed no oral absorption at all, for example the acetoxymethyl ester of Cloxacillin.
It is an object of this invention to provide acyloxymethyl esters of particularly potent cephalosporin antibiotics, which esters are substantially totally absorbed orally, whereas the parent cephalosporin acids from which they are derived are essentially completely unabsorbed. It is a further object of the present invention to provide esters having additional desirable qualities, such as crystallinity and extended stability for example, which the parent cephalosporin acids normally do not possess.
USPTO Backgrounds
USPTO Backgrounds