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Venous leg ulcers affect approximately 1% of the general population and 3.6% of those over the age of 65. The goal of the research described herein is to shorten the time to healing by developing wound care alternatives that are based on a comprehensive understanding of the venous ulcer wound environment. The proteolytic and inflammatory components in wound fluids and tissue biopsy samples were characterized in subjects with documented long-standing venous ulcers that had showed resistance to standard therapy. All wounds showed polymicrobial colonization with greater than 10(6) CFU/g. Myeloperoxidase, a measure of leukocyte infiltration, was also markedly elevated in these wounds. Zymography revealed the presence of both pro-matrix metalloproteinase (MMP)-2 and pro-MMP-9 in wound fluids and to a lesser extent in tissue biopsies. Using an immunocapture activity assay we reveal a sevenfold excess of MMP-9 in wound fluid as compared to tissue, with 73% in the activated form. In contrast, MMP-8 total protein levels were nearly equal in wound fluids and biopsies. Fibronectin, a critical component of the extracellular matrix, was shown to be degraded in both wound fluids and biopsy samples. Finally, the potential of a novel wound dressing to neutralize several constituents of this hostile wound environment is shown.

Efficient schemes for selective N-protection of 1,4,7-triazacyclononane and I ,5,9-triazacyclododecane and for synthesis of related bis-coronands are based upon the synthetic intermediacy of tricyclic orthoamides.

1,5,9-Triazacyclododecane and related macrocyclic triamines can be conveniently constructed around a single carbon atom as template; this route permits the preparation of selectively alkylated derivatives.

There is a growing interest in the development of wound dressings that possess functionality beyond providing physical protection and an optimal moisture environment for the wound. To this end, a novel dressing material based on a sulfonated triblock polymer has been developed. This versatile polymer possesses an ion-exchange capability that is amenable to binding and controlled release of a variety of therapeutic agents. This sulfonated polymer offers several advantages over existing commercial hydrogels used as wound dressings. These include (1) hydrophilicity that is proportional to sulfonation level, (2) easy preparation of fabric supported dressings (e.g., polyester, cotton, nylon), (3) excellent mechanical integrity of the materials when hydrated, (4) stability to a variety of chemistries, and (5) stability to a variety of sterilization methodologies. In this study, polymer was coated onto a polyester fabric and then modified by ion exchange to prepare the sodium, silver, or doxycycline salts. These sulfonated triblock polymer formulations were then evaluated for their capacity to sequester the neutrophil proteases, elastase, and collagenase-2 (MMP-8). Several of the formulations were found to sequester significant amounts of either elastase or collagenase. These formulations were demonstrated to be tested against a commercially available dressing that is currently marketed for its protease-inhibiting capability. The experimental dressing was statistically superior to the commercial dressing at inhibiting MMP-8 and elastase under the same conditions.

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The cyclic triamines (Ia) and (IIa) react with DMF dimethyl acetal (III), forming the tricyclic orthoamides (IV).