Glycopeptide Antibiotic Derivatives with Cleavable Linkers
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Solution Overview
Problem
Glycopeptide and lipoglycopeptide antibiotics face challenges with poor solubility, leading to localized side effects and the need for large volumes for administration, which limits their effectiveness in emergency situations and exposes patients to inflammatory responses like phlebitis and the 'Red-Man' syndrome.
Innovation Solution
Derivatives with altered ionization states are developed, featuring ionically charged groups attached via linkers that can be cleaved under physiological conditions, enhancing solubility and reducing side effects by masking the antibiotic during administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glycopeptide antibiotics are administered at high concentrations to ensure effective treatment, then antibacterial activity is improved, but inflammatory side effects such as phlebitis and Red-Man syndrome increase
Solution Approach 1:
The patent introduces a solubilizing agent as an intermediary substance that forms a complex with the glycopeptide antibiotic. This intermediary complex masks the antibiotic during administration, reducing its direct interaction with blood vessels and tissues, thereby decreasing inflammatory side effects while maintaining antibacterial activity through controlled release
Solution Approach 2:
The patent changes the physical-chemical parameters of the glycopeptide antibiotic by forming a complex with a solubilizing agent. This alteration in molecular structure and physical properties improves solubility and allows for reduced administration volumes at lower concentrations, thereby reducing harmful inflammatory responses while preserving therapeutic efficacy
2Stability of the object's composition
If large volumes of glycopeptide antibiotic solution are administered to improve solubility, then solubility is improved, but the administration volume increases leading to prolonged infusion time
Solution Approach 1:
The solubilizing agent acts as an intermediary that forms a soluble complex with the glycopeptide antibiotic, enabling improved solubility without requiring large volumes of administration solution. This complex can be dissolved in smaller volumes, thereby reducing infusion time while maintaining stability
Solution Approach 2:
The patent creates a composite system by combining the glycopeptide antibiotic with a solubilizing agent to form a soluble complex. This composite material has improved solubility properties and can be administered in reduced volumes, addressing both solubility requirements and time efficiency
3Object-affected harmful factors
If glycopeptide antibiotics are administered in reduced volumes to decrease side effects, then side effects are reduced, but solubility becomes insufficient for effective administration
Solution Approach 1:
The solubilizing agent serves as a mediator that enables the glycopeptide antibiotic to be administered in reduced volumes. By forming a soluble complex, it maintains adequate solubility even at lower concentrations, thereby reducing side effects while preserving necessary solubility for effective administration
Solution Approach 2:
The patent modifies the physical-chemical parameters of the antibiotic system by introducing a solubilizing agent that changes the solubility characteristics. This allows the antibiotic to be administered in reduced volumes at lower concentrations while maintaining sufficient solubility, thereby reducing side effects without compromising administration feasibility
4Stability of the object's composition
If poly(ethylene glycol) chains are added to glycopeptides to improve solubility, then solubility is improved, but the molecular size increases significantly
Solution Approach 1:
Instead of directly modifying the glycopeptide structure with large poly(ethylene glycol) chains, the patent uses a solubilizing agent as an intermediary that forms a complex with the antibiotic. This approach improves solubility without significantly increasing the molecular size of the active antibiotic component, as the solubilizing agent remains separate or forms a manageable complex
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 derivatives exhibit improved solubility and reduced side effects, allowing for effective treatment of infections with reduced volume administration while maintaining antibacterial properties against resistant strains.
Implementation Method 1
derivatives of glycopeptide and lipoglycopeptide antibiotics possessing an altered ionization state
Implementation Method 2
ionically charged groups attached via linkers that can be cleaved under physiological conditions, enhancing solubility
Implementation Method 3
linkers that can be cleaved under physiological conditions
Data Source
AI summary
The invention relates to derivatives of glycopeptide and lipoglycopeptide antibiotics possessing an altered ionization state with respect to the parent glycopeptide or lipoglycopeptide antibiotic, and having the ability to be regenerated as the parent glycopeptide or lipoglycopeptide antibiotic under physiological conditions. These compounds are useful as antibiotics for the prevention and/or the treatment of bacterial infections.