Wound dressing for the controlled release of therapeutic agents comprising also an inhibitor of a protease enzyme & a linker group cleavable by such an enzyme

A wound dressing material for controlled activation of a wound healing therapeutic compound in the presence of a protease enzyme in a wound fluid, the material comprising: a medically acceptable polymer; a wound healing therapeutic agent; an inhibitor of the protease enzyme; and a linker group which is cleavable by the protease enzyme, wherein the activities of both the wound healing therapeutic agent and the inhibitor are increased by contacting the wound dressing material with a wound fluid containing the protease enzyme. The polymer may be cross-linked to the linker group; the wound healing therapeutic agent and/or the inhibitor may be conjugated to the medically acceptable polymer by the linker group; or the wound healing therapeutic agent may be conjugated to the inhibitor by the linker group. The therapeutic agent may be a reactive oxygen scavenger (ie antioxidant), an antimicrobial agent (eg antibiotic), a pain relieving agent (eg anti-inflammatory), an antiseptic, an analgesic, a local anaesthetic, or a growth factor. The enzyme inhibitor may be selected from the group consisting of Tissue inhibitor of Metalloproteinase (TIMP), 4-(2-aminoethyl)benzenesulfonyl fluoride AEBSF, antithrombin, (p-Amidinophenyl)methanesulfonyl fluoride APMSF, Aprotinin, diisopropylfluorophospate DFP, phenyl methyl sulfonyl fluoride PMSF, Antipain, Chymostatin, Leupeptin, Tosyl-lysine chloromethylketone TLCK, Tosyl-phenyl chloromethylketone TPCK, L-trans-epoxysuccinylleucylamido (4-guanidino) butane E-64, Amastatin, Bestatin, Diprotin, Ethylenediamine tetra-acetic acid (EDTA), pepstatin and mixtures thereof. Preferably, the enzyme may be a matrix metalloproteinase, the therapeutic agent may be a reactive oxygen scavenger, and the inhibitor may be a tissue inhibitor or metalloproteinase (TIMP).