Compositions and methods for the treatment and prophylaxis of surgical site infections
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Publication Number
US-11975101-B2
Publication Date
2024-05-07
Expiration Date
Abstract
The present invention provides methods for preventing, inhibiting or treating a surgical site infection associated with a surgical operation comprising the step of applying to the surgical site a biocompatible, biodegradable substrate being impregnated and/or having its surface coated fully or partially with a matrix composition which provides local controlled and prolonged release of at least one pharmaceutically active agent at the surgical site.
Core Innovation
The disclosed invention relates to biodegradable, biocompatible substrates for prophylaxis of soft-tissue incision site infection associated with abdominal surgery. The approach administers directly to the soft-tissue incision site β-tricalcium phosphate (β-TCP) particles that are impregnated and/or have their surface coated fully or partially with a matrix composition. The matrix composition is engineered to provide local controlled, prolonged drug release at the site.
The matrix composition includes a biodegradable polymer, a first lipid component comprising at least one sterol that is non-covalently associated with the biodegradable polymer, and a second lipid component comprising at least one phospholipid having fatty acid moieties of at least 12 carbons. The lipid components form a highly organized lipid-saturated matrix/substantially water-resistant continuous structure. This organization is presented as enabling sustained drug release, including zero-order kinetics behavior with at least 30% drug release under hydration.
The matrix composition further comprises a pharmaceutically active agent, including an antibiotic agent for the prophylaxis method. The provided formulation examples include tetracyclines such as doxycycline, and the document also describes additional pharmaceutically active agents such as antiseptics, anti-inflammatory agents, and anti-fungal agents.
Claims Coverage
The partial content includes one independent claim directed to prophylaxis of a soft-tissue incision site infection associated with abdominal surgery by administering directly to the incision site β-TCP particles impregnated and/or coated with a specific lipid-associated, biodegradable polymer matrix containing an antibiotic agent. The independent claim is refined by dependent claims that specify antibiotic class, sterol identity, quantitative release behavior, and composition weight-percent ranges, with additional narrowing to resistant bacteria such as MRSA.
Direct incision-site administration of lipid-matrix coated β-TCP particles
Administering directly to the soft-tissue incision site β-tricalcium phosphate (β-TCP) particles that are impregnated or have their surface coated fully or partially with a matrix composition.
Biodegradable polymer with non-covalently associated sterol lipid component
The matrix composition comprises a biodegradable polymer, and a first lipid component comprising at least one sterol non-covalently associated with the biodegradable polymer.
Phospholipid with at least 12-carbon fatty acid moieties as second lipid component
The matrix composition comprises a second lipid component comprising at least one phospholipid having fatty acid moieties of at least 12 carbons.
Antibiotic-agent loaded structured matrix composition for prophylaxis
The matrix composition comprises an antibiotic agent.
Across the independent claim and dependent refinements, the inventive coverage centers on direct prophylactic administration of impregnated/coated β-TCP particles using a matrix that combines a biodegradable polymer with a non-covalently associated sterol lipid component and a phospholipid component with fatty-acid moieties of at least 12 carbons, with an antibiotic agent for infection prophylaxis. The dependent claims further narrow antibiotic selection, sterol identity, sustained-release performance, and composition weight-percent ranges.
Stated Advantages
Provides local controlled, prolonged drug release at the incision site.
Enables sustained release including zero-order kinetics behavior, with at least 30% drug release under hydration conditions as stated.
Supports biofilm eradication and/or biofilm formation inhibition in the described MBEC™ assay context.
Documented Applications
Prophylaxis of soft-tissue incision site infection associated with abdominal surgery by directly administering β-TCP particles impregnated or surface coated with the defined lipid/biodegradable polymer antibiotic matrix.
Preclinical incision-site infection evaluation in an intramuscular SSI rat model using S. aureus, comparing a TCP coated with doxycycline matrix versus controls, as described.
Biofilm-related evaluation using an MBEC™ assay, where coated TCP matrix exhibits biofilm eradication/inhibition versus free doxycycline or TCP alone, as described.
Sternal wound site infection/mediastinitis testing in rabbits using TCP matrix/doxycycline-coated particles, as described.
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