Methods of treating fungal infections
Inventors
Millenbaugh, Nancy • Gleaton, Jeremy Wesley • Kirui, Dickson Kiprono • Snyder, Sabrina • Rock, Crystal
Assignees
General Dynamics Information Technology Inc • US Department of Navy
Publication Number
US-11524051-B2
Publication Date
2022-12-13
Expiration Date
2038-02-27
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Abstract
Methods of treating a fungal infection in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a composition comprising one or more antifungal peptides selected from the group consisting of BmKn2, dBmKn2, Kn2-7, and dKn2-7 are described. Antifungal pharmaceutical compositions and dosage forms, including field-deployable dosage forms, comprising one or more of these antifungal peptides are also described.
Core Innovation
The invention relates to methods of treating fungal infections in subjects by administering therapeutically effective amounts of compositions comprising one or more antifungal peptides selected from BmKn2, dBmKn2, Kn2-7, and dKn2-7. These peptides can be used alone or combined with other pharmaceutically acceptable agents and formulated in pharmaceutical compositions including topical dosage forms such as wound dressings and field-deployable forms.
Fungal infections are challenging to eradicate due to their potential to rapidly progress into invasive or systemic diseases, the need for long treatment durations, and associated high morbidity and mortality, especially among immunocompromised and vulnerable populations. The difficulty is compounded by the similarity between fungal and mammalian cells leading to side effects of current antifungals, fungal biofilms reducing susceptibility to treatments, rise in drug-resistant fungal species, limited approved antifungals, and insufficient new drug development.
The invention addresses these problems by discovering that the scorpion venom-derived peptides BmKn2 and Kn2-7, including their D-amino acid forms (dBmKn2, dKn2-7), possess growth inhibitory, fungicidal, and anti-biofilm activity against Candida albicans. These peptides provide novel antifungal agents that may be synthetically produced with improved stability in D-forms, can be used to inhibit planktonic and biofilm fungal infections including drug-resistant strains, and incorporated into pharmaceutical compositions that enhance treatment options for fungal infections including wound and polymicrobial infections.
Claims Coverage
The patent includes one independent pharmaceutical composition claim and one independent method claim. The main inventive features cover antifungal peptide compositions and their use in treating fungal or polymicrobial infections.
Pharmaceutical composition comprising specific antifungal peptides
A pharmaceutical composition comprising one or more peptides selected from Kn2-7, dKn2-7, BmKn2, and dBmKn2, wherein the BmKn2 and Kn2-7 peptides comprise a combination of D form and L form amino acids; the composition further comprises pharmaceutically acceptable carriers, excipients or diluents, and contains peptide amounts sufficient to treat a fungal infection in a subject.
Dosage form and formulation features for topical administration
Topical dosage forms of the pharmaceutical composition include wound dressings, specifically field-deployable wound dressings, which may comprise electrospun and/or wet-spun fibers made from polysaccharides such as 2% alginate alone or combined with 0.1% or 0.2% chitosan oligosaccharide lactate.
Method of treating fungal and polymicrobial infections
A method of treating a polymicrobial infection and/or a fungal infection in a subject by administering the pharmaceutical compositions as described, employing therapeutically effective peptide amounts.
The independent claims cover pharmaceutical compositions with defined antifungal peptides and pharmaceutically acceptable carriers, dosage forms suitable for topical and field-deployable use, and methods of treating fungal and polymicrobial infections using these compositions.
Stated Advantages
The peptides Kn2-7 and dKn2-7 exhibit extremely low hemolytic activity compared to other peptides tested, indicating a good safety profile and reduced toxicity to red blood cells.
D-form amino acid peptides, such as dKn2-7, have increased stability against serum proteases, which may lead to improved in vivo bioavailability and efficacy.
The peptides effectively inhibit growth and kill planktonic fungi and exhibit potent activity against pre-formed fungal biofilms, including drug-resistant strains of Candida albicans.
Pharmaceutical compositions including these peptides can be formulated for controlled and extended release, allowing sustained therapeutic levels and improved clinical efficacy.
The peptides are suitable for inclusion in field-deployable dosage forms, such as wound dressings, that are stable under room temperature conditions and provide long shelf life.
Documented Applications
Treating fungal infections in subjects, particularly those caused by Candida albicans and drug-resistant strains.
Treating polymicrobial infections that include fungal infections, including wound infections with biofilm-associated fungi and bacteria.
Use in pharmaceutical compositions for topical administration, including wound dressings and field-deployable dressings for battlefield or remote healthcare settings.
Incorporation into dosage forms comprising electrospun and wet-spun fibers including polysaccharide-based materials for controlled and extended release of antifungal peptides.
Treatment of fungal infections in various body sites including skin, bloodstream, deep tissue, oral cavity, ocular cavity, gastrointestinal tract, and urinary tract.
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