High molecular weight polymer-based prodrugs
AssigneeEnzon, Inc.
InventorsRichard B. Greenwald, Annapurna Pendri
Life of this patent
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Abstract
High molecular weight, water-soluble prodrugs of the formula: ##STR1## wherein: D is a biologically active moiety; M is X or Q; X is an electron withdrawing group; Q is a moiety containing a free electron pair positioned five or six atoms from Y'; Y and Y' are oxygen or sulfur; R is a polyalkylene oxide; and Z is OH, C.sub.1-4 all moieties or ##STR2## are disclosed. In preferred embodiments, the prodrugs contain a polyethylene glycol having a molecular weight of at least about 20,000.
Claims44
A composition comprising the formula:
- ##STR28## wherein:
- D is a residue of a biologically active moiety having undergone an esterification reaction;
- M is X or Q;
- X is an electron withdrawing group;
- Q is a moiety containing a free electron pair positioned five or six atoms from Y';
- Y and Y' are independently O or S;
- R is a substantially non-antigenic polymer.
A method of preparing a composition of the formula:
- ##STR32## wherein:
- D is a biologically active moiety;
- M is X or Q;
- X is an electron withdrawing group;
- Q is a moiety containing a free electron pair positioned five or six atoms from Y';
- Y and Y' are independently O or S;
- and
- R is a polyalkylene oxide;
- comprising reacting a biologically active moiety, D, with a polymer of the formula:
- ##STR33## wherein:
- 2 M, R, Y, Y' and the same as above;
- and
- at least one of Z' and Z.sup.2 is OH, under conditions sufficient to cause attachment of said polymer to said biologically-active moiety via an ester linkage.
A composition comprising the formula:
- ##STR35## wherein:
- D is a residue of a biologically active moiety having undergone an esterification reaction;
- M is X or Q;
- X is an electron withdrawing group;
- Q is a moiety containing a free electron pair positioned five or six atoms from Y';
- Y and Y' are independently O or S;
- R is a substantially non-antigenic polymer;
- and
- Z.sup.3 is ##STR36## wherein D" is selected from the group consisting of dialkyl ureas, OC.sub.1-4 alkyl moieties or carboxylic acids.
A method of preparing a composition of the formula:
- ##STR37## wherein:
- D is a biologically active moiety;
- M is X or Q;
- X is an electron withdrawing group;
- Q is a moiety containing a free electron pair positioned five or six atoms from Y';
- Y and Y' are independently O or S;
- R is a polyalkylene oxide;
- and
- Z.sup.3 is ##STR38## wherein D" is selected from the group consisting of dialkyl ureas, C.sub.1-4 alkyl moieties or carboxylic acids, comprising:
- reacting a biologically active moiety, D, with a polymer of the formula:
- ##STR39## wherein:
- M, R, Y, Y' and the same as above;
- and
- Z' and Z.sup.2 are OH,
- under conditions sufficient to cause attachment of said polymer to said biologically-active moiety via an ester linkage which displaces one of Z' and Z.sup.2 and converts the other Z moiety to Z.sup.3.
A composition comprising the formula:
- ##STR40## wherein:
- M is X or Q;
- X is an electron withdrawing group;
- Q is a moiety containing a free electron pair positioned five or six atoms from Y';
- Y and Y' are independently O or S;
- R is a substantially non-antigenic polymer.
Dependencies are inferred from the claim text.