KLA Peptide Conjugates for Oral Biodrug Absorption Enhancement
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Solution Overview
Problem
Existing peptide-based gastrointestinal permeation enhancers face challenges in enhancing oral drug absorption due to cytotoxicity and susceptibility to digestive enzymes, leading to potential systemic side effects and limited clinical trial applications.
Innovation Solution
Development of multi-arm polyethylene glycol-KLA peptide conjugates, PEGylated distearoyl phosphatidylethanolamine-KLA peptide conjugates, and polyamidoamine dendrimer-polyethylene glycol-KLA peptide conjugates that modulate tight junctions for enhanced drug absorption while reducing cytotoxicity and enzyme resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If peptide-based gastrointestinal permeation enhancers are used to enhance oral drug absorption, then drug absorption is improved, but cytotoxicity and susceptibility to digestive enzymes increase
Solution Approach 1:
The patent applies composite materials by combining peptide-based permeation enhancers with protective carriers or modifying the peptide structure to create a composite system that maintains absorption-enhancing properties while reducing cytotoxicity and enzyme susceptibility through the protective matrix or structural modification
2Productivity
If peptide-based gastrointestinal permeation enhancers are used to enhance oral drug absorption, then drug absorption is improved, but susceptibility to digestive enzymes increases
Solution Approach 1:
The patent uses an intermediary approach by introducing protective carriers, polymers, or structural modifications that act as mediators between the peptide enhancer and digestive enzymes, shielding the peptide from enzymatic degradation while allowing it to maintain its absorption-enhancing function
3Productivity
If tight junctions are loosened to enhance permeation, then drug absorption is improved, but systemic side effects increase due to over-permeability
Solution Approach 1:
The patent applies partial action by using controlled, moderate loosening of tight junctions rather than complete disruption, achieving sufficient drug absorption while avoiding excessive permeability that would lead to systemic side effects, endotoxemia, or inflammatory responses
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
These conjugates significantly enhance the absorption of biodrugs in the gastrointestinal tract, increasing bioavailability and stability, thus addressing the limitations of existing peptide-based enhancers.
Implementation Method 1
these conjugates can significantly enhance the absorption of orally administered biodrugs in the gastrointestinal tract by exhibiting the property of opening the tight junctions of gastrointestinal tract membrane cells
Implementation Method 2
must ensure stability against digestive enzymes so as not to be decomposed by digestive enzymes in the gastrointestinal tract
Data Source
Figure 1
Figure 2A
Figure 2B~3A
AI summary
The present invention relates to, for oral delivery of biodrugs, a multi-arm polyethylene glycol-KLA peptide conjugate, a PEGylated distearoyl phosphatidylethanolamine-KLA peptide conjugate, a PAMAM dendrimer-KLAL peptide conjugate, and a composition for enhancing absorption, in the gastrointestinal tract, of a biodrug for oral administration containing same as oral absorption enhancers, the conjugates of the present invention reducing cytotoxicity due to the cell permeable properties of a KLA peptide, and maintaining a tight junction modulation function of KLA through effects such as increasing resistance to proteolytic enzymes in the gastrointestinal tract, so as to promote gastrointestinal absorption of biodrugs such as peptides, proteins, polysaccharides, and antibodies when orally administrated, and thus being able to be usefully employed in increasing the bioavailability of a drug.