Adiponectin Peptidomimetic Formulation Stabilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a high unmet need for effective and safe therapies for dry eye and ocular diseases associated with inflammation, as existing treatments are limited in efficacy and stability of low molecular weight adiponectin peptidomimetics.
Innovation Solution
A composition comprising a therapeutically effective amount of a 1 kDa to 2 kDa adiponectin peptidomimetic, a generally recognized as safe solubilizer, one or more generally recognized as safe surfactants, a generally recognized as safe buffer, optionally boric acid and optionally mannitol, with osmolality between 260 to 330 mOsm/kg and pH between 4.5 to 5.5.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If low molecular weight adiponectin peptidomimetics are used to treat dry eye and ocular inflammation, then therapeutic efficacy is improved, but the peptides are susceptible to degradation by fragmentation, deamidation, oxidation and hydrolysis
Solution Approach 1:
The patent applies parameter changes by optimizing pH (4.5-5.5), osmolality (260-330 mOsm/kg), and temperature conditions to stabilize the peptide. The formulation uses specific buffer systems and excipients to control chemical parameters that prevent degradation pathways including deamidation, oxidation, and hydrolysis while maintaining therapeutic efficacy.
Solution Approach 2:
The patent employs intermediary substances including surfactants, solubilizers, and stabilizing excipients that act as mediators between the peptide and the environment. These intermediaries protect the peptide from direct exposure to degrading conditions while allowing the therapeutic agent to remain bioactive and effective.
2Quantity of substance
If the peptide concentration is increased to achieve therapeutically relevant concentrations, then solubilization is improved, but aggregation of peptide due to loss/fragmentation of hydrophilic sequences occurs
Solution Approach 1:
Surfactants and solubilizing excipients serve as intermediaries that enable higher peptide concentrations to be achieved without aggregation. These substances interact with the hydrophobic regions of the peptide, preventing intermolecular aggregation while maintaining solubility and therapeutic concentration levels.
Solution Approach 2:
The formulation optimizes ionic strength, pH, and the presence of specific excipients to alter the physicochemical parameters of the solution. These parameter changes reduce the tendency of peptide molecules to aggregate even at higher concentrations by modifying electrostatic interactions and solvation characteristics.
3Reliability
If pH is increased to higher levels, then deamidation of peptide occurs which converts positively-charged peptide to neutral peptide, but this leads to micro-collapse of peptide chains and resultant precipitation
Solution Approach 1:
The patent precisely controls pH within the range of 4.5-5.5 using buffer systems. This parameter optimization prevents excessive deamidation that would eliminate the positive charge, while also preventing precipitation by maintaining conditions where the peptide remains soluble and structurally intact.
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 stabilizes the adiponectin peptidomimetics, preventing aggregation and degradation, while maintaining non-irritating properties, thereby providing therapeutic benefits for dry eye and ocular inflammation.
Implementation Method 1
solubilization into therapeutically relevant peptide concentrations
Implementation Method 2
one or more generally recognized as safe surfactants
Implementation Method 3
a generally recognized as safe buffer, optionally boric acid and optionally mannitol; wherein the osmolality is between 260 to 330 mOsm/kg and the pH is between 4.5 to 5.5
Implementation Method 4
the challenges in developing a formulation strategy for these small peptides requires a balance of physiochemical variables that would allow chemical stabilization into a peptide drug product
Data Source
AI summary
Disclosed are compositions and methods for the use of adiponectin peptidomimetics in therapeutic applications. The compositions can include a peptide, for example, D-Asn-Ile-Pro-Nva-Leu-Tyr-D-Ser-Phe-Ala-D-Ser-NH2, a solubilizer, a surfactant(s), a buffer, optionally boric acid and optionally mannitol. The osmolality of the composition can be between 260 to 330 mOsm/kg and the pH can be between 4.5 to 5.5. Methods of using the compositions in treating certain eye disease(s) are also disclosed.