pH-Responsive Fecal Microbiota Capsules for Targeted Intestinal Release
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Solution Overview
Problem
Current treatments for Clostridium difficile infection (CDI) are inadequate, particularly for recurrent cases, and existing faecal microbiota transplantation methods face challenges in ensuring the viability and targeted delivery of microbiota to the intestine, with high recurrence rates and potential adverse effects from human cell impurities in donor stool.
Innovation Solution
A pharmaceutical composition comprising a powdered lyophilized faecal microbiota in a pH-responsive capsule, encapsulated with a coating shell for delayed release in the large intestine, ensuring high viability and targeted delivery of colony-forming units (CFU) while minimizing human DNA content below 1%, using a method that includes stool collection, homogenization, filtration, centrifugation, cryoprotectant addition, lyophilization, and encapsulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If faecal microbiota transplantation is performed using homogenized stool or extracts, then treatment of CDI can be achieved, but human cell impurities in donor stool may cause adverse effects and reduced reliability
Solution Approach 1:
The patent extracts and removes human cell impurities from the donor stool through a systematic processing procedure involving homogenization, filtration, and centrifugation steps. This isolation of the harmful component (human cells) from the beneficial microbiota resolves the contradiction by eliminating adverse effects while preserving treatment reliability.
Solution Approach 2:
The patent applies parameter changes by controlling the physical and chemical properties of the stool sample during processing. By adjusting parameters such as particle size through filtration, density through centrifugation, and moisture content through lyophilization, the patent optimizes the microbiota preparation to remove human cells while maintaining high viability of beneficial bacteria.
2Ease of operation
If conventional faecal microbiota transplantation methods are used, then treatment can be administered, but targeted delivery to the large intestine is not ensured
Solution Approach 1:
The patent introduces an enteric coating as an intermediary substance between the microbiota capsule and the gastrointestinal environment. This coating acts as a mediator that protects the microbiota during passage through the stomach and small intestine, and selectively dissolves in the large intestine to enable targeted delivery. This resolves the contradiction by maintaining ease of oral administration while achieving precise anatomical targeting.
Solution Approach 2:
The patent applies local quality by creating different properties in different parts of the administration system. The enteric coating has acid-resistant properties in the upper GI tract and dissolution properties in the lower GI tract, enabling the same capsule to navigate easily through the digestive system while releasing contents only at the target location (large intestine).
3Reliability
If antibiotics are used to treat CDI, then initial infection can be managed, but high recurrence rates occur
Solution Approach 1:
The patent converts the harm caused by antibiotic use (disruption of normal microbiota leading to recurrence) into a benefit by administering a concentrated, purified microbiota preparation that actively restores the gut ecosystem. The processed microbiota acts as a beneficial force that counteracts the negative effects of antibiotic treatment and prevents recurrence, effectively transforming the problem of microbiota depletion into a solution.
Solution Approach 2:
The patent applies preliminary action by restoring the gut microbiota before recurrence can occur. By administering a high concentration of viable, purified microbiota immediately after antibiotic treatment, the patent proactively establishes a protective microbial barrier that prevents pathogen recolonization, rather than waiting for recurrence to happen and then treating it.
4Manufacturing precision
If stool is processed with extensive handling, then human cell impurities are removed, but viability of colony forming units may be reduced
Solution Approach 1:
The patent utilizes phase transitions, specifically lyophilization (freeze-drying), to remove water from the microbiota preparation without subjecting it to high temperatures or harsh chemical treatments. This phase change from liquid to solid state allows for effective concentration and purification of the microbiota while preserving the viability of colony-forming units, resolving the contradiction between thorough processing and maintaining biological activity.
Solution Approach 2:
The patent replaces harsh mechanical or chemical processing methods with gentler techniques. Instead of using high-temperature sterilization or strong chemical treatments that could damage viable bacteria, the patent employs controlled centrifugation, filtration, and lyophilization - milder processes that achieve purification while maintaining CFU viability.
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 composition effectively reduces CDI recurrence, potentially eliminating the need for antibiotics, with superior efficacy in recurrent cases compared to standard treatments, and demonstrates safe, accessible, and easy administration with minimal side effects.
Implementation Method 1
a pH responsive polymer composition and may dissolve or provide a delayed release of the processed faecal composition to the intestine of the patient
Implementation Method 2
The processed faecal composition is a powdered lyophilized faecal composition
Data Source
Figure 1
AI summary
Pharmaceutical composition in the form of a capsule for oral administration comprising a encapsulated processed faecal composition that comprises faecal microbiota, characterized in that, the processed faecal composition is a powdered lyophilized faecal composition that is encapsulated with a coating shell which is a pH responsive polymer composition and may dissolve or provide a delayed release of the processed faecal composition to the intestine, and wherein the processed faecal composition comprises faecal microbiota comprising colony forming units (CFU) and equal to or less than 1% of human DNA with respect to the total DNA. Method of preparation of the pharmaceutical composition.