High molecular weight polymer-based prodrugs

DETAILED DESCRIPTION OF THE INVENTION A.
THE PRODRUGS In most aspects of the invention, the prodrug compositions of the present invention contain hydrolyzable linkages between the polymer portion and a biologically active moiety derived from a biologically active moiety or nucleophile, i.
e.
native or unmodified drug.
These linkages are preferably ester linkages designed to hydrolyze at a rate which generates sufficient amounts of the biologically active parent compound in a suitable time period so that therapeutic levels of the parent therapeutic moiety or moieties are delivered prior to excretion from or inactivation by the body.
The term "sufficient amounts" for purposes of the present invention shall mean an amount which achieves a therapeutic effect as such effect is understood by those of ordinary skill in the art.
In one preferred embodiment of the invention, the prodrug compositions of the invention comprise the formula set forth below: ##STR6## wherein: D is a residue of a biologically active moiety; X is an electron withdrawing group; Y and Y' are independently O or S; (n) is zero (0) or a positive integer, preferably from 1 to about 12; R.
sub.
1 and R.
sub.
2 are independently selected from the group consisting of H, C.
sub.
1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls and substituted C.
sub.
1-6 alkyls; p1 R.
sub.
3 is a substantially non-antigenic polymer, C.
sub.
1-12 straight or branched alkyl or substituted alkyl, C.
sub.
5-8 cycloalkyl or substituted cycloalkyl, carboxyalkyl, carboalkoxy alkyl, dialkylaminoalkyl, phenylalkyl, phenylaryl or ##STR7## R.
sub.
4 and R.
sub.
5 are independently selected from the group consisting of H, C.
sub.
1-6 alkyls, aryls, substituted aryls, aralkyls, heteroalkyls, substituted heteroalkyls, and substituted C.
sub.
1-6 alkyls or jointly form a cyclic C.
sub.
5 -C.
sub.
7 ring.
Preferably, the polymer portion, designated R.
sub.
3 herein, is further substituted with a terninal capping moiety (Z) which is distal to the primary linkage attaching D to the polymer