Method and compositions for inhibiting or preventing adverse effects of oral antibiotics
Inventors
Kaleko, Michael • Connelly, Sheila • Wacher, Vincent John
Assignees
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Publication Number
US-11596674-B2
Publication Date
2023-03-07
Expiration Date
Abstract
This invention provides, in part, various compositions and methods for protecting the gastrointestinal microbiome from antibiotic disruption.
Core Innovation
The invention relates to beta-lactamase formulations for use during oral antibiotic therapy to address antibiotic-associated adverse effects. The formulations include particles or pellets containing a specified low percentage of beta-lactamase together with hydroxypropylmethylcellulose acetate succinate (HPMCAS), ethylcellulose dispersion, sodium stearyl fumarate, buffer, trehalose, and a high water fraction.
The invention further specifies beta-lactamase as comprising an amino acid sequence with at least 95% identity with sequences selected from SEQ ID NO: 1 and SEQ ID NO: 5. Certain dependent formulations additionally define the buffer as sodium hydrogen phosphate.
In addition, the invention covers methods of preventing an antibiotic-associated adverse effect by administering the beta-lactamase formulation to a subject receiving an oral beta-lactamase substrate antibiotic. The adverse effect is identified as Clostridium difficile infection or antibiotic-associated diarrhea.
Claims Coverage
The independent claims identified are clm-00001 and clm-00007. Across these independent claims, the inventive features include a defined particle or pellet formulation with a specified low beta-lactamase content, excipient composition, and high water fraction, and beta-lactamase sequence identity constraints relative to SEQ ID NO: 1 and SEQ ID NO: 5.
Low-beta-lactamase particle formulation with defined excipient composition and high water fraction
A beta-lactamase formulation comprising at least one particle, each particle comprising about 0.1–1% beta-lactamase, about 0.1–1% hydroxypropylmethylcellulose acetate succinate (HPMCAS), about 5–15% ethylcellulose dispersion, about 0.1–1% sodium stearyl fumarate, about 0.1–1% buffer, about 0.5–35 trehalose, and about 80–90% water.
Sequence-identity constrained beta-lactamase pellet formulation with defined excipient composition and high water fraction
A beta-lactamase formulation comprising at least one pellet, each pellet comprising about 0.5% by weight beta-lactamase, the beta-lactamase comprising an amino acid sequence having at least 95% identity with the amino acid sequence selected from SEQ ID NO: 1 and SEQ ID NO: 5, about 0.3% HPMCAS, about 10.1% ethylcellulose dispersion, about 0.2% sodium stearyl fumarate, about 0.1% buffer, about 1.0% trehalose, and about 88.8% water.
Independent claim coverage focuses on beta-lactamase formulations in which particle or pellet compositions are defined by low beta-lactamase percentages, specific excipient ranges, and high water fractions, and the beta-lactamase sequence is constrained by identity to sequences selected from SEQ ID NO: 1 and SEQ ID NO: 5.
Stated Advantages
Preventing an antibiotic-associated adverse effect in a subject receiving an oral beta-lactamase substrate antibiotic.
Prevention of Clostridium difficile infection.
Prevention of antibiotic-associated diarrhea.
Documented Applications
Prevention of antibiotic-associated adverse effects during oral antibiotic therapy using an oral beta-lactamase substrate antibiotic.
Prevention of Clostridium difficile infection.
Prevention of antibiotic-associated diarrhea.
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