Methods of treating fungal infections
Inventors
Millenbaugh, Nancy • Gleaton, Jeremy Wesley • Kirui, Dickson Kiprono
Assignees
Publication Number
US-10548948-B2
Publication Date
2020-02-04
Expiration Date
2038-02-27
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Abstract
Antifungal pharmaceutical compositions, dosage forms, and methods of use thereof are disclosed.
Core Innovation
The invention relates to methods of treating fungal infections in subjects by administering a therapeutically effective amount of a pharmaceutical composition comprising one or more peptides selected from the group consisting of BmKn2, dBmKn2, Kn2-7, and dKn2-7. These peptides may comprise D-form amino acids and can be used to treat planktonic or biofilm fungal infections, including pre-formed biofilms. The compositions also contemplate treatment of fungal infections resistant to conventional antifungal agents and wound infections.
Fungal infections present significant challenges due to their ability to rapidly evolve into invasive or systemic diseases requiring prolonged treatment. Existing antifungal therapeutics often target similar molecules in mammalian cells, causing severe side effects and limiting dosing. Furthermore, fungal biofilms reduce susceptibility to conventional agents. The rise of drug-resistant Candida species and limited new antifungal drugs underscore the need for novel antifungal agents and treatment methods.
The inventors discovered that peptides BmKn2 and Kn2-7, derived from scorpion venom, possess antifungal properties, including growth inhibition, fungicidal activity, and efficacy against biofilms in Candida albicans in vitro. Production of these peptides with D-form amino acids enhances stability and therapeutic potential. The invention provides methods and pharmaceutical compositions using these peptides alone or combined with additional pharmaceutically acceptable agents to treat fungal infections, polymicrobial infections, and promote wound healing.
Claims Coverage
The claims include one independent claim specifically targeting a method of treating fungal infections using compositions comprising antifungal peptides, with various dependent claims covering additional features and embodiments.
Method of treating fungal infections with selected peptides
A method of treating a fungal infection by administering a therapeutically effective amount of a pharmaceutical composition comprising one or more peptides selected from BmKn2, dBmKn2, Kn2-7, and dKn2-7, wherein BmKn2 and Kn2-7 comprise combinations of D and L form amino acids.
Treatment of antifungal-resistant infections
The method applies to fungal infections resistant to one or more conventional antifungal agents.
Treatment of planktonic or biofilm fungal infections
The fungal infection treated can be planktonic, biofilm, or a combination, including pre-formed biofilms.
Treatment of wound infections
The method encompasses treating wound infections by administering the peptide-containing pharmaceutical compositions.
Combination therapy with additional pharmaceutically acceptable agents
The pharmaceutical composition may be administered alone or in combination with additional agents selected from antimicrobials, analgesics, wound healing agents, biofilm dispersal agents, or biofilm inhibitors, where antimicrobials include antifungal, antibacterial, or antiviral agents.
Use of dKn2-7 peptide specifically
The method includes embodiments where the peptide administered is specifically dKn2-7.
Treatment of Candida infections
The fungal infection to be treated includes infections caused by Candida, particularly Candida albicans.
Use of alginate as wound healing agent
The additional pharmaceutically acceptable wound healing agent can be an alginate.
The claims define a method of treating fungal infections using therapeutic peptides derived from scorpion venom with particular attention to D-form amino acid peptides, covering treatment of resistant fungal infections, biofilms, wound infections, use in combination with other agents, and targeting Candida species.
Stated Advantages
The D-form amino acid peptides demonstrate increased stability against proteolytic degradation compared to L-forms, enhancing therapeutic efficacy.
The peptides, especially Kn2-7 and dKn2-7, have potent antifungal activity against planktonic and biofilm forms of Candida albicans, including drug-resistant strains.
Kn2-7 and dKn2-7 exhibit low hemolytic activity, indicating a favorable safety profile with reduced toxicity to human red blood cells.
The peptides can be incorporated into various pharmaceutical compositions and dosage forms, including field-deployable topical wound dressings, offering practical administration options.
Documented Applications
Treatment of fungal infections comprising planktonic or biofilm fungal infections, including pre-formed biofilms in human or animal subjects.
Treatment of fungal infections resistant to conventional antifungal agents.
Treatment of wound infections, including cutaneous and subcutaneous wounds, acute and chronic wounds.
Treatment of polymicrobial infections comprising fungal and bacterial or viral co-infections.
Use of pharmaceutical compositions comprising antifungal peptides alone or combined with additional antimicrobial, analgesic, wound healing, biofilm dispersal, or biofilm inhibitory agents.
Incorporation of antifungal peptides into topical dosage forms such as creams, ointments, patches, films, bandages, or electrospun nanofibrous dressings that are field-deployable.
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