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Publication Number
US-11517614-B2
Publication Date
2022-12-06
Expiration Date
Abstract
This invention provides, in part, various compositions and methods for protecting the gastrointestinal microbiome from antibiotic disruption from orally administered antibiotics.
Core Innovation
The invention relates to protecting a subject’s gastrointestinal (GI) microbiome from disruption caused by an orally administered beta-lactam antibiotic by administering a formulation comprising a beta-lactamase capable of deactivating the oral antibiotic in the GI tract. The formulation is described as reducing disruption caused by residual or excess oral antibiotic while minimizing interference with systemic antibiotic activity.
A central aspect is an enterically coated capsule comprising an enterically coated pellet, with a nested pellet-in-capsule arrangement and an enteric polymer coating. The capsule is coated with FS EUDRAGIT FS 30 D, and the formulation is designed to provide GI-delivered beta-lactamase that deactivates antibiotic in distal GI regions while limiting proximal beta-lactamase leakage that could degrade antibiotic prior to absorption.
The beta-lactamase is described as capable of deactivating beta-lactam antibiotics, with examples including P1A, P2A, P3A, P4A, and SYN-004. The document also describes optional beta-lactamase inhibitors such as clavulanic acid and alternative beta-lactamase delivery approaches via genetically modified microorganisms, including recombinant yeast secreting beta-lactamase for delivery in the distal small intestine or colon.
Claims Coverage
The provided independent claim material describes one independent method claim directed to protecting a subject’s GI microbiome from an oral antibiotic using a beta-lactamase delivered in an enterically coated capsule and enterically coated pellet. The inventive features center on the GI-protective method, the defined pellet and coating components, and constraints on systemic interference and release location.
Enterically coated capsule comprising an enterically coated pellet with defined pellet excipients and enteric coating
Administering a formulation comprising a beta-lactamase capable of deactivating the oral antibiotic, wherein the formulation comprises an enterically coated capsule comprising an enterically coated pellet, the pellet comprising about 20% to 25% sucrose sphere, about 30% to 40% binder excipient, about 12% to 18% beta-lactamase, about 1% to 2% buffer salts, about 0.5% to 3% plasticizer, about 15% to 30% EUDRAGIT coating, optionally about 0.5% to about 1.5% KH2PO4 and about 2.5% to 5% HPMC 603; and wherein the capsule is coated with FS EUDRAGIT FS 30 D.
Beta-lactamase deactivating an oral antibiotic for GI microbiome protection
Administering a formulation comprising a beta-lactamase capable of deactivating the oral antibiotic to a subject who is undergoing treatment or has recently undergone treatment with the oral antibiotic, thereby protecting the subject’s gastrointestinal (GI) microbiome from an oral antibiotic.
Functional constraint of not substantially interfering with plasma levels
Characterizing that the beta-lactamase does not substantially interfere with plasma levels of a systemically absorbed orally administered antibiotic.
Distal release location relative to antibiotic release
Formulating the beta-lactamase to be released in the GI tract at a location distal to where the orally administered antibiotic is released.
Across the provided material, the claim coverage centers on a GI microbiome-protection method using an enterically coated capsule and enterically coated pellet that contain beta-lactamase to deactivate an oral beta-lactam antibiotic in the GI tract. The covered concept is coupled to specific excipient and EUDRAGIT-based coating components and to constraints directed to avoiding substantial systemic interference and achieving distal GI release relative to antibiotic release.
Stated Advantages
Protecting the subject’s gastrointestinal (GI) microbiome from an oral antibiotic.
Deactivating residual or excess oral antibiotic in the GI tract without substantially interfering with systemic antibiotic activity.
Preventing GI microbiome disruption while limiting beta-lactamase leakage that would otherwise degrade antibiotic before absorption.
Does not substantially interfere with plasma levels of a systemically absorbed orally administered antibiotic.
Documented Applications
Treating or preventing antibiotic-induced adverse effect via microbiome-mediated disorders.
Treating or preventing C. difficile infection (CDI) and C. difficile-associated disease.
Treating or preventing ulcerative colitis.
Treating or preventing Crohn’s disease.
Treating or preventing irritable bowel syndrome.
Protecting a subject’s GI microbiome from an oral antibiotic during treatment or after recent treatment.
C. difficile (CDI) prevention studies and microbiome-protection studies are described in the provided summary.
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