Sustained Release Formulation Using Temperature-Responsive Amino Acid Matrix
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Peptide and small molecule drugs often have short half-lives due to rapid renal clearance and enzymatic degradation, leading to the need for high doses and variable plasma levels, making them impractical for pharmaceutical use.
Innovation Solution
A sustained release pharmaceutical formulation comprising a therapeutic agent with an amino acid sequence capable of forming a reversible matrix at body temperature, formed from hydrogen bonds and hydrophobic interactions, which slows absorption into circulation, thereby extending half-life and stabilizing plasma levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If peptide and small molecule drugs are administered to improve therapeutic effectiveness, then the half-life is short due to rapid renal clearance and enzymatic degradation, but high doses are required which cause side effects such as nausea
Solution Approach 1:
The invention changes the physical-chemical parameters of the drug delivery system by using a temperature-responsive amino acid sequence that forms a reversible matrix at body temperature. This matrix controls the release rate of the active agent, transforming the delivery kinetics from rapid clearance to sustained release, thereby extending half-life and reducing peak concentrations that cause side effects
Solution Approach 2:
The amino acid sequence acts as an intermediary between the active agent and the biological system. It forms a reversible matrix that mediates the release of the active agent, protecting it from rapid renal clearance and enzymatic degradation while controlling its absorption into circulation, thus extending half-life without requiring high doses
2Duration of action of moving object
If high doses of peptide drugs are administered to counter short half-life, then the half-life is extended, but nausea and other side effects occur
Solution Approach 1:
The invention changes the release kinetics parameter by using a temperature-responsive matrix that maintains the active agent at lower concentrations for extended periods. This avoids the high peak concentrations associated with high-dose administration that trigger nausea, while still achieving extended half-life through controlled sustained release
Solution Approach 2:
The reversible matrix formed by the amino acid sequence serves as an intermediary that buffers the release of the active agent. It prevents sudden high concentrations from reaching the circulation, thereby eliminating nausea while maintaining extended half-life through controlled release kinetics
3Stability of the object's composition
If peptide drugs are administered to achieve therapeutic effect, then plasma levels are variable due to short half-life, but consistent plasma levels are needed for effective treatment
Solution Approach 1:
The invention ensures continuous therapeutic action by using a temperature-responsive matrix that provides sustained release of the active agent. The matrix continuously releases the agent at controlled rates, maintaining stable plasma levels over an extended period and eliminating the variability associated with short half-life drugs that require frequent dosing
Solution Approach 2:
The invention changes the temporal distribution parameter of drug concentration by using a reversible matrix with temperature-responsive release kinetics. This transforms the concentration-time profile from rapid peaks and troughs to a sustained, stable release pattern, achieving consistent plasma levels without extending the inherent half-life of the active agent
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 formulation achieves a desirable pharmacokinetic profile with a flat peak-to-trough ratio and long Tmax, allowing for less frequent administration and improved stability of peptide and small molecule drugs.
Implementation Method 1
The reversible matrix is formed from hydrogen bonds (e.g., intra- and/or intermolecular hydrogen bonds) as well as from hydrophobic contributions
Implementation Method 2
The reversible matrix is formed from hydrogen bonds (e.g., intra- and/or intermolecular hydrogen bonds) as well as from hydrophobic contributions
Implementation Method 3
the amino acid sequence may exhibit a visible and reversible inverse phase transition with the selected formulation. That is, the amino acid sequence may be structurally disordered and highly soluble in the formulation below a transition temperature (Tt), but exhibit a sharp (2-3°C range) disorder-to-order phase transition when the temperature of the formulation is raised above the Tt
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention provides pharmaceutical formulations for sustained release, and methods for delivering a treatment regimen with a combination of sustained release and long half-life formulations. The invention provides improved pharmacokinetics for peptide and small molecule drugs. A sustained release pharmaceutical formulation comprises a therapeutic agent for systemic administration, where the therapeutic agent comprises an active agent and an amino acid sequence capable of forming a reversible matrix at the body temperature of the subject.