Bismuth-thiol compositions and methods for treating wounds
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Publication Number
US-11974978-B2
Publication Date
2024-05-07
Expiration Date
Abstract
The invention relates to bismuth-thiol compounds and pharmaceutical preparations thereof. The invention further relates to methods for treating a topical wound, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a bismuth-thiol compound, wherein the composition is applied to the infection. Methods for treating microbial infections such as diabetic foot infections are also provided.
Core Innovation
The invention relates to treating, managing, or preventing a bacterial infection in a subject by administering a liposome-free pharmaceutical composition comprising a suspension of microparticles that include a bismuth-thiol (BT) compound selected from a specified group. The microparticles have defined particle-size distribution characteristics expressed using D90, D50, and D10 values.
The disclosed treatment is described in infection and wound healing contexts in which biofilms are present or targeted, including bacterial and fungal biofilms. The liposome-free BT microparticle compositions are administered directly to infected wounds, including diabetic foot infection and diabetic foot ulcer, and the patent text describes wound healing and wound closure or size reduction within about 12 weeks.
The document further describes therapeutic effects including reduction or dispersal of bacterial and fungal biofilms, inhibition of biofilm formation, growth, invasiveness, and reformation after debridement. It also describes inhibition of planktonic cell viability and growth and inhibition of exotoxin secretion, with supportive clinical evaluation using DFI wound score, ulcer size assessment using 3D digital photographs, and microbiological and biofilm endpoints.
Claims Coverage
The independent claim coverage centers on administering a therapeutically effective liposome-free BT microparticle suspension for bacterial infection, with two core inventive features: the defined BT-containing microparticle composition and the specified particle-size distribution constraints.
Treating, managing, or preventing bacterial infection with liposome-free BT microparticles
Administering to the subject a therapeutically effective amount of a liposome-free composition comprising a suspension of microparticles including a bismuth-thiol (BT) compound selected from the specified BT compound group.
Microparticle size distribution defined by D90, D50, and D10 constraints
Microparticles having a D90 of less than 2 µm, a D50 of less than or equal to 0.72 µm to 1.3 µm, and/or a D10 of less than or equal to 0.33 µm to 0.70 µm.
Biofilm-focused treatment effects
Providing treatment that includes at least one of reducing or dispersing bacterial biofilms, impairing bacterial biofilm growth or formation, or preventing bacterial biofilm reformation or spread.
Bacterial infection defined by specified causative species
Limiting the bacterial infection to be caused by one or more bacteria selected from the specified bacterial species set, including Staphylococcus aureus and MRSA among others.
Optional additional antibiotic agent selection
Selecting one or more additional agents from an enumerated group of antibiotic agents.
The coverage is directed to administering a therapeutically effective, liposome-free BT microparticle suspension for bacterial infection, where the BT compound is selected from a defined list and the microparticle size distribution is constrained by D90, D50, and D10 values, with additional biofilm-related, species-defined, and antibiotic-agent features.
Stated Advantages
Reducing or dispersing bacterial and fungal biofilms.
Impairing bacterial biofilm growth or formation.
Preventing bacterial biofilm reformation or spread after debridement.
Inhibiting growth and exotoxin secretion.
Wound healing and wound closure within about 12 weeks.
Reduced ulcer size.
Reduced risk of amputation or infection-related surgery.
Improved wound-size reduction and lower amputation/surgery rates in a Phase 1b/2a topical BT clinical study with systemic antibiotics.
Wound healed or substantially healed within about 12 weeks.
Reduced need for amputation and infection-related surgery.
Wound closure and wound size reduction/elimination.
Inhibition of planktonic cell viability and growth.
Reductions in reinfection/relapse at EOS and lower target-ulcer-related amputations vs placebo.
Potential biofilm reduction at EOT using biofilm score comparisons.
Good tolerability with minimal systemic bismuth exposure.
Documented Applications
Topical treatment for diabetic foot infections and/or diabetic foot ulcers or wounds, including reducing or dispersing biofilms and supporting wound healing.
Combination therapy contexts for diabetic foot infections, including use with standard and non-standard diabetic foot infection therapies.
Preclinical mouse model applications, including assessment outcomes such as reduced wound and spleen bioburden and biofilm-related readouts.
A Phase 1b/2a clinical study application for topical BT in combination with systemic antibiotics, reporting improved wound-size reduction and lower amputation/surgery rates.
Topical treatment in a clinical trial setting for diabetic foot infection, with BisEDT administered and evaluated against placebo using DFI wound scoring, ulcer size assessment using 3D digital photographs, and microbiological and biofilm endpoints.
Topical treatment of infected wounds, including diabetic foot infections and diabetic foot ulcers, by administering liposome-free BT microparticle compositions directly to the infection or ulcer site.
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