Oral Delivery of Viable Cells Using Bile Binding Agents
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Solution Overview
Problem
Current oral delivery methods for live bacterial vaccines face challenges such as stability issues during storage, sensitivity to gastric acid, and effectiveness in reaching the intestinal environment, leading to reduced efficacy.
Innovation Solution
Incorporating a bile binding agent, specifically cholestyramine, into dried viable bacterial vaccine cell formulations to protect against bile acid toxicity and enhance survival in the intestinal tract, combined with an enteric coating for acid protection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If dried viable bacterial cells are administered orally, then stability during storage is improved, but sensitivity to gastric acid and bile acids increases, reducing survival in the intestinal tract
Solution Approach 1:
The patent introduces an enteric coating as an intermediary layer between the dried bacterial cells and the harsh intestinal environment. This coating acts as a protective barrier that prevents direct contact with bile acids and gastric acid, allowing the cells to survive the transit through the gastrointestinal tract while maintaining their dried stable state during storage.
Solution Approach 2:
The patent creates a composite formulation by combining dried viable bacterial cells with an enteric coating material. This composite structure integrates the storage stability of the dried cells with the protective properties of the enteric coating, resulting in a formulation that survives both storage conditions and the harsh intestinal environment.
2Reliability
If enteric coating is used to protect bacteria from gastric acid, then survival through stomach acid is improved, but effectiveness in reaching the intestinal environment is reduced due to premature release or degradation
Solution Approach 1:
The patent utilizes pH-dependent parameter changes of the enteric coating material. The coating is designed to remain intact in the acidic stomach environment (low pH) but dissolves or degrades in the less acidic intestinal environment (higher pH). This parameter change allows the coating to provide protection where needed while releasing the bacteria in the target location.
Solution Approach 2:
The enteric coating is designed with dynamic properties that allow it to change its state based on environmental conditions. It transitions from a protective barrier in the stomach to a dissolving layer in the intestine, enabling the system to adapt its function based on the location and conditions within the gastrointestinal tract.
3Productivity
If high doses of bacteria are administered, then therapeutic effect is improved, but cost and complexity of delivery system increases
Solution Approach 1:
The patent employs a simple, cost-effective enteric coating formulation that can be applied to existing tablet or capsule structures. Rather than using complex engineered delivery systems, the invention uses a relatively simple coating material that provides effective protection, making the overall delivery system more affordable and easier to manufacture while achieving the desired therapeutic effect.
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
Significantly increases the survival and efficacy of dried viable bacterial cells in the intestinal tract, allowing for improved immune response and therapeutic outcomes by protecting against bile acids and gastric acid.
Implementation Method 1
the incorporation of small amounts of a bile binding agent into formulations of dried viable cells significantly increases the survival of the cells in the intestinal tract. According to the invention, the bile binding agent is cholestyramine
Implementation Method 2
An 'enteric' coating may be used to avoid the death of the live bacterial formulations in gastric acid. An enteric coating is a polymer layer that will not dissolve in acidic conditions
Data Source
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AI summary
This invention relates to solid formulations for the oral delivery of live microbial cells which comprise dried viable cells and small amounts of a bile acid binding agent, for example, an anion exchange resin such as cholestyramine. The presence of bile acid binding agents in the formulation significantly increases the survival of the cells in the intestinal tract and facilitates delivery of the viable cells to the intestine.