Methods of treating fungal infections
Inventors
Millenbaugh, Nancy • Gleaton, Jeremy Wesley • Kirui, Dickson Kiprono
Assignees
Publication Number
US-10946065-B2
Publication Date
2021-03-16
Expiration Date
2038-02-27
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Abstract
The invention relates to 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. Antifungal pharmaceutical compositions and dosage forms, including field-deployable dosage forms, comprising one or more of these antifungal peptides are also contemplated herein.
Core Innovation
The invention relates to methods of treating fungal infections in subjects by administering a therapeutically effective amount of compositions comprising one or more antifungal peptides selected from BmKn2, dBmKn2, Kn2-7, and dKn2-7. These peptides may include D-form amino acids and are effective against fungal infections including planktonic and biofilm forms, including pre-formed biofilms. The methods also cover treating polymicrobial infections comprising fungal and additional microbial infections, and compositions may be administered alone or with other pharmaceutically acceptable agents such as antimicrobials, analgesics, wound healing agents, biofilm dispersal agents, or biofilm inhibitors.
Fungal infections present significant challenges including difficulty in eradication, high morbidity and mortality, especially in vulnerable populations such as immunocompromised, neonates, and burn patients. Candida species are the most common cause of fungal infections with high mortality rates. Biofilms formed by fungi reduce susceptibility to conventional antifungals, and eukaryotic fungal cells share molecular targets with mammalian cells, causing side effects and dosing limitations. Drug resistance among fungal species and a limited pipeline of new antifungal drugs underscore the need for new agents and methods.
The invention discovers that the peptides derived from scorpion venom, specifically BmKn2 and Kn2-7, and their D-amino acid variants have antifungal activity including growth inhibition, fungicidal, and anti-biofilm activity against Candida albicans. These peptides can be synthetically produced with D-amino acids to improve stability against proteolytic degradation. The methods include pharmaceutical compositions comprising these peptides, alone or in combination with other agents, usable in various dosage forms including topical and injectable, with further applications in field-deployable wound dressings.
Claims Coverage
The patent contains one independent claim focused on a method of treating polymicrobial infections with specific peptide compositions, covering various features of the peptides and formulations.
Method of treating polymicrobial infections with specific antifungal peptides
A method of treating a polymicrobial infection in a subject 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 the peptides comprise a combination of D and L form amino acids.
Treatment of resistant polymicrobial infections
The method covers polymicrobial infections resistant to one or more conventional antimicrobial drugs, including antifungal resistant infections.
Treatment targeting pathogenic fungi and additional microbes
The polymicrobial infection includes infection with one or more pathogenic fungi from a specified group (e.g., Candida albicans) and one or more additional microbes such as bacteria and/or viruses.
Treatment of fungal infections in various forms
The fungal infection targeted may be planktonic or biofilm, including pre-formed biofilms.
Treatment of wound infections
The method encompasses treating polymicrobial infections present in wound infections.
Use of specific peptides and combination therapies
The method specifically contemplates the use of dKn2-7 peptide, and administration either alone or in combination with additional pharmaceutically acceptable agents such as antimicrobials, analgesics, anesthetics, anti-inflammatories, hemostatic agents, immunomodulators, wound healing agents, biofilm dispersal or inhibitor agents.
The claims cover therapeutic methods employing antifungal peptides BmKn2, dBmKn2, Kn2-7, and dKn2-7 with embodiments addressing resistant infections, various infection types including biofilms and wounds, and combinations with other agents, highlighting peptide stereochemistry and formulation versatility.
Stated Advantages
The peptides, especially the D-form variants, have increased stability against proteases, improving bioavailability and efficacy in vivo.
The peptides demonstrate potent antifungal activity including growth inhibition, fungicidal effects, and anti-biofilm activity against Candida albicans, including strains resistant to conventional antifungal agents.
Kn2-7 and dKn2-7 peptides exhibit extremely low hemolytic activity, indicating a good safety profile and less toxicity towards human red blood cells.
The peptides can be formulated into various pharmaceutical compositions and dosage forms, including field-deployable wound dressings, which can be stored and transported under room temperature conditions.
Combination therapies with additional pharmaceutically acceptable agents may reduce required doses and treatment durations, potentially enhancing therapeutic outcomes.
Documented Applications
Use of the antifungal peptides to treat fungal infections, including planktonic, biofilm, pre-formed biofilm fungal infections, and fungal infections resistant to conventional antifungals.
Treatment of polymicrobial infections comprising fungal pathogens alongside bacteria and/or viruses.
Treatment of wound infections, including cutaneous and subcutaneous wounds, acute and chronic wounds, burns, and other tissue injuries.
Incorporation of antifungal peptides into pharmaceutical compositions for topical, injectable, oral, nasal, ocular, and other routes of administration.
Formulation of peptides into field-deployable dosage forms such as wound dressings, gauzes, patches, bandages, and other medical dressing materials for use in remote or battlefield environments.
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