Rectal Bile Acid Composition for Localized GLP-1 Secretion
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Solution Overview
Problem
Current treatments for obesity and diabetes lack effective methods for non-systemic delivery of enteroendocrine peptide secretion enhancing agents to the lower ileum, colon, and rectum, which are crucial for modulating glucose and insulin levels and appetite regulation.
Innovation Solution
A pharmaceutical composition comprising a therapeutically effective amount of an enteroendocrine peptide secretion enhancing agent, such as bile acids or bile salts, combined with an absorption inhibitor and a carrier, specifically designed for non-systemic rectal or colonic delivery, using a formulation like suppositories, enema solutions, or rectal foams to target the lower ileum, colon, and rectum.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enteroendocrine peptide secretion enhancing agents are administered systemically, then therapeutic effects are achieved, but systemic side effects and loss of localized therapeutic action occur
Solution Approach 1:
The invention divides the gastrointestinal tract into specific target segments (distal ileum, colon, rectum) and delivers the bile acid composition specifically to these segments using rectal or colonic administration routes. This segmentation allows localized therapeutic action on enteroendocrine L-cells in the distal GI tract without systemic distribution, resolving the contradiction between achieving therapeutic effect and avoiding systemic side effects.
Solution Approach 2:
The invention applies local quality by concentrating the therapeutic agent (bile acid composition) specifically in the distal gastrointestinal tract where enteroendocrine L-cells are located. The rectal or colonic administration ensures high local concentration at the target site while minimizing systemic absorption, thereby achieving reliable therapeutic effect locally without generating harmful systemic effects.
2Ease of operation
If conventional oral delivery methods are used, then administration is simple, but the agent is absorbed in the upper digestive tract and fails to reach the lower ileum, colon, and rectum effectively
Solution Approach 1:
Instead of the conventional oral route that delivers agents from the upper to lower digestive tract (where premature absorption occurs), the invention inverts the administration approach by using rectal or colonic routes. This reverse delivery method bypasses the upper digestive tract absorption barrier and directly deposits the bile acid composition in the target region (distal ileum, colon, rectum), achieving both ease of administration and precise target delivery.
3Manufacturing precision
If the composition is designed for non-systemic delivery, then therapeutic localization is improved, but formulation complexity increases
Solution Approach 1:
The invention uses rectal or colonic administration as an intermediary route that naturally provides localized delivery to the distal gastrointestinal tract. This intermediary approach leverages the existing anatomical and physiological characteristics of rectal/colonic absorption to achieve precise localization without requiring complex controlled-release mechanisms or sophisticated delivery devices, thereby balancing delivery localization with formulation simplicity.
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 enhances the secretion of peptides like GLP-1 and PYY, reducing food intake and glucose levels, thereby treating obesity and diabetes by localizing the delivery to the distal gastrointestinal tract, minimizing systemic absorption and maximizing therapeutic effect.
Implementation Method 1
Katsuma S et al. (Biochem Biophys Res Commun., vol. 329, no. 1, April 2005, pages 386-390) disclose that bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1.
Implementation Method 2
a. a therapeutically effective amount of an enteroendocrine peptide secretion enhancing agent; b. an absorption inhibitor of the enteroendocrine peptide secretion enhancing agent
Data Source
Figure 1A~1B
Figure 2
Figure 3
AI summary
Provided herein are methods and compositions for treating metabolic diseases and conditions associated with metabolic diseases.