Water-Soluble Lipidated Peptide Salts for Inflammatory Disease Treatment
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Solution Overview
Problem
Lipidated peptides and peptido-mimetics have low aqueous solubility, classified as Class IV drugs, which hinders their development due to poor water solubility, limiting their effectiveness in treating diseases mediated by Pellino-1 induced inflammatory signal transduction complexes.
Innovation Solution
Development of novel water-soluble salts of lipidated peptides and peptido-mimetics, such as sodium, potassium, or lithium salts, which significantly enhance their aqueous solubility, allowing for improved formulation and administration routes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If lipidated peptides and peptido-mimetics are used as drug candidates, then therapeutic effectiveness against inflammatory diseases is improved, but aqueous solubility deteriorates (Class IV drugs)
Solution Approach 1:
The patent applies parameter changes by converting the chemical form of lipidated peptides from neutral or hydrophobic forms to water-soluble salt forms (e.g., sodium salts, potassium salts, ammonium salts). This chemical modification changes the solubility parameter while preserving the therapeutic activity, allowing the compound to transition from Class IV (low solubility) to a more favorable solubility class for pharmaceutical development.
Solution Approach 2:
The patent uses salt-forming agents (counterions such as Na+, K+, NH4+) as intermediaries to bridge the hydrophobic lipidated peptide structure and the hydrophilic aqueous environment. These intermediary ions associate with the peptide to form soluble salt complexes, enabling the hydrophobic active ingredient to dissolve in water-based pharmaceutical formulations without altering the core therapeutic structure.
2Reliability
If lipidated peptides are formulated for pharmaceutical use, then disease treatment capability is improved, but formulation complexity increases due to solubility limitations
Solution Approach 1:
By changing the formulation parameter from using the parent lipidated peptide to using its water-soluble salt derivative, the patent simplifies the formulation process. The salt forms can be directly dissolved in aqueous media to create stable formulations, eliminating the need for complex co-solvent systems, surfactants, or special delivery vehicles that would otherwise be required to solubilize the hydrophobic parent compound.
3Reliability
If high concentration solutions are prepared, then therapeutic efficacy is improved, but solubility limitations prevent achievement of high concentrations
Solution Approach 1:
The patent resolves this contradiction by changing the chemical parameter of the active ingredient to its salt form, which has dramatically enhanced aqueous solubility (up to 50,000-fold increase). This parameter change enables the preparation of high-concentration solutions that would be impossible with the parent compound, thereby achieving the desired therapeutic efficacy through higher bioavailable concentrations of the active ingredient.
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 water-soluble salts exhibit up to 50,000-fold increased solubility, enabling the preparation of high-concentration solutions and stable pharmaceutical compositions for effective treatment of inflammatory diseases and disorders, including inflammatory bowel diseases, autoimmune diseases, and others.
Implementation Method 1
water soluble salts of Formula I, e.g., substantially pure compound of Formula I, wherein M is an alkaline metal cation or ammonium
Data Source
AI summary
Provided herein are water soluble salts of Formula I, wherein R1, A, and M are defined herein. Also provided herein are methods of preparing the salts of Formula I and methods of using the same.