Nucryst Pharmaceuticals Corp.

Rita Johanna Mary Langford

Robert Edward Burrell

Stojan Djokic

Hua Qing Yin

The invention provides bioabsorbable materials with antimicrobial coatings or powders which provide an effective and sustainable antimicrobial effect. Specifically, this invention provides bioabsorbable materials comprising a bioabsorbable substrate associated with one or more antimicrobial metals being in a crystalline form characterized by sufficient atomic disorder, such that the bioabsorbable material in contact with an alcohol or water based electrolyte, releases atoms, ion, molecules, or clusters of at least one antimicrobial metal at a concentration sufficient to provide an antimicrobial effect. The one or more antimicrobial metals do not interfere with the bioabsorption of the bioabsorbable material, and do not leave behind particulates larger than 2 &mgr;m, as measured 24 hours after the bioabsorbable material has disappeared. Most preferably, the particulate sizing from the coating or powder is sub-micron that is less than about 1 &mgr;m, as measured 24 hours after the bioabsorbable material has disappeared. Particulates are thus sized to avoid deleterious immune responses or toxic effects. Such antimicrobial metals are in the form of a continuous or discontinuous coating, a powder, or a coating on a bioabsorbable powder. The antimicrobial coating is thin, preferably less than 900 nm or more preferably less than 500 nm, and very fine grained, with a grain size (crystallite size) of preferably less than 100 nm, more preferably less than 40 nm, and most preferably less than 20 nm. The antimicrobial coating is formed of an antimicrobial metal, which is overall crystalline, but which is created with atomic disorder, and preferably also having either or both of a) a high oxygen content, as evidenced by a rest potential greater than about 225 mV, more preferably greater than about 250 mV, in 0.15 M Na CO against a SCE (standard calomel electrode), or b) discontinuity in the coating. The antimicrobial metal associated with the bioabsorbable substrate may also be in the form of a powder, having a particle size of less than 100 &mgr;m, or preferably less than 40 &mgr;m, and with a grain size (crystallite size) of preferably less than 100 nm, more preferably less than 40 nm, and most preferably less than 20 nm. Such powders may be prepared as a coating preferably of the above thickness, onto powdered biocompatible and bioabsorbable substrates; as a nanocrystalline coating and converted into a powder; or as a powder of the antimicrobial metal which is cold worked to impart atomic disorder. Methods of preparing the above antimicrobial bioabsorbable materials are thus also provided.

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Edmonton, Canada

Rita Johanna Mary Langford