Methods and compositions for disrupting biofilm utilizing chitosan-derivative compounds
Inventors
Baker, Shenda M. • Wiesmann, William P. • Townsend, Stacy Marie
Assignees
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Publication Number
US-12465616-B2
Publication Date
2025-11-11
Expiration Date
Abstract
Described herein are methods of disrupting (e.g., reducing the viscosity of, or dissolving) a preformed biofilm in a subject, the method comprising: administering to the subject an effective amount of a composition comprising a soluble chitosan or derivatized chitosan wherein the soluble chitosan or derivatized chitosan when administered contacts the preformed biofilm, thereby disrupting (e.g., reducing the viscosity of, or dissolving) the preformed biofilm.
Core Innovation
The invention relates to derivatized chitosan compositions defined by chitosan of formula (I), with each R1 independently selected from hydrogen, acetyl, and a group of formula (II). The distribution of R1 substituents is constrained such that at least 25% of R1 substituents are H, at least 1% are acetyl, and 4-30% of R1 substituents are a group of formula (II), and the derivatized chitosan has a molecular weight between 10,000 and 150,000 Da and a polydispersity index (PDI) between 1.5 and 2.5.
A method is provided for disrupting a preformed biofilm in a subject infected with specified bacteria by administering, by inhalation, a therapeutically effective amount of a composition comprising a derivatized chitosan. Upon administration, the composition disrupts the preformed biofilm in the respiratory system of the subject and reduces the viscosity of sputum in the respiratory system relative to the sputum prior to administration.
The disclosure also describes formula (II) as encompassing amino/guanidino functionality, including amino-acid-based substituents, and includes representative amino-acid side chains such as arginine, lysine, and histidine. It further frames the approach in respiratory, gastrointestinal tract, and wound infection contexts, and describes combination use with antibiotic, anti-inflammatory, and mucolytic compounds.
Claims Coverage
The independent claim coverage centers on two inventive features: inhalation administration of a derivatized chitosan composition for respiratory biofilm disruption and sputum viscosity reduction, and the defined chitosan composition limits for formula (I), substituent distribution, molecular weight, and PDI.
Inhalation administration of derivatized chitosan for respiratory biofilm disruption and sputum viscosity reduction
Administering to the subject by inhalation a therapeutically effective amount of a composition comprising a derivatized chitosan, wherein upon administration the composition disrupts the preformed biofilm in the respiratory system of the subject and reduces the viscosity of sputum in the respiratory system of the subject relative to the sputum prior to administration of the composition.
Derivatized chitosan of formula (I) with constrained R1 substituent distribution
Providing a derivatized chitosan comprising a chitosan of formula (I) in which n is an integer between 20 and 6000, each R1 is independently selected from hydrogen, acetyl, and a group of formula (II), wherein at least 25% of R1 substituents are H, at least 1% of R1 substituents are acetyl, and 4-30% of R1 substituents are a group of formula (II).
Defined molecular weight and polydispersity index of derivatized chitosan
Requiring that the molecular weight of the derivatized chitosan is between 10,000 and 150,000 Da and that the polydispersity index (PDI) of the derivatized chitosan is between 1.5 and 2.5.
Overall, the independent claim ties respiratory inhalation therapy to a derivatized chitosan composition defined by formula (I) R1 distribution, molecular weight, and PDI ranges, with the stated therapeutic outcomes of preformed biofilm disruption and reduction of sputum viscosity relative to pre-administration sputum.
Stated Advantages
Disrupts the preformed biofilm in the respiratory system of the subject.
Reduces the viscosity of sputum in the respiratory system of the subject relative to sputum prior to administration of the composition.
Documented Applications
Method of disrupting a preformed biofilm in the respiratory system of a subject infected with specified bacteria, including administration by inhalation of a therapeutically effective amount of a derivatized chitosan composition.
Treatment or prevention of gastrointestinal tract infections using the described derivatized chitosan compositions, including effects on biofilm and viscosity.
Treatment or prevention of wound infections using the described derivatized chitosan compositions, including effects on biofilm and viscosity.
Application to a subject having cystic fibrosis.
Combination administration including administering an antibiotic, anti-inflammatory, or mucolytic compound in conjunction with, prior to, or subsequent to the administration of the composition.
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