Beta-lactamase Formulations for Microbiome Protection
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Solution Overview
Problem
Current antibiotic treatments can disrupt the balance of the human microbiome in the gastrointestinal tract, leading to conditions such as Clostridium difficile infection and antibiotic-associated diarrhea, due to the inactivation of beta-lactam antibiotics by bacterial enzymes like beta-lactamases.
Innovation Solution
Development of modified-release formulations of beta-lactamases, such as P3A, which are designed to release substantially in the gastrointestinal tract, either encapsulated within core particles or coated with a delayed-release coating like Eudragit, to inactivate excess antibiotics and maintain microbiome balance without interfering with systemic antibiotic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If beta-lactam antibiotics are administered to treat bacterial infections, then the therapeutic effect against pathogenic bacteria is improved, but the balance of normal intestinal microbiota is disrupted leading to C. difficile infection and antibiotic-associated diarrhea
Solution Approach 1:
The patent extracts and removes excess beta-lactam antibiotics from the gastrointestinal tract using beta-lactamase enzymes. The enzyme preparation specifically targets and inactivates unabsorbed antibiotics in the gut, separating the therapeutic action from the harmful side effects on microbiota
Solution Approach 2:
The patent introduces beta-lactamase enzymes as an intermediary substance that mediates between the administered antibiotics and the intestinal microbiota. The enzymes act as a protective layer that neutralizes excess antibiotics before they can harm the microbiome, allowing continued antibiotic therapy while preventing microbiome disruption
2Stability of the object's composition
If beta-lactamases are administered to protect microbiota, then the balance of normal intestinal microbiota is maintained, but the enzymes must be released specifically in the GI tract without interfering with systemic antibiotic efficacy
Solution Approach 1:
The patent applies delayed-release coating technology to beta-lactamase enzymes before administration. This preliminary action ensures the enzymes remain stable in the stomach and are released only when they reach the gastrointestinal tract, preventing premature degradation and ensuring targeted delivery
Solution Approach 2:
The patent creates localized enzyme activity specifically in the gastrointestinal tract through targeted release mechanisms. The beta-lactamases are concentrated where needed (in the gut lumen) rather than distributed systemically, providing local protection to microbiota without affecting overall antibiotic pharmacokinetics
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The modified-release beta-lactamase formulations effectively prevent C. difficile infection and other antibiotic-induced adverse effects by ensuring the beta-lactamases are released in the GI tract, thereby maintaining the balance of normal intestinal microbiota and reducing the risk of antibiotic resistance.
Implementation Method 1
the delayed-release coating is substantially stable in gastric fluid
Implementation Method 2
the delayed-release coating comprises a Eudragit compound
Implementation Method 3
beta-lactamases are bacterial defensive enzymes that hydrolyze beta-lactam antibiotics
Implementation Method 4
beta-lactamases are able to efficiently catalyze the irreversible hydrolysis of the amide bond of the beta-lactam ring
Data Source
AI summary
The present invention provides, in part, formulations comprising a beta-lactamase. Particularly, modified-release formulations comprising a beta-lactamase are provided which release a substantial amount of the beta-lactamase in the intestines. Therapeutic uses of the beta-lactamase formulations are also provided.