Colloidal Suspension for Prolonged Protein Release
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Solution Overview
Problem
Current pharmaceutical formulations for prolonged release of therapeutic proteins and peptides face challenges such as short plasma half-life, toxicity, immunogenicity, and rapid release, leading to fluctuating plasma concentrations and adverse effects.
Innovation Solution
Aqueous colloidal suspensions of low viscosity comprising submicronic particles of water-soluble biodegradable polymers with hydrophobic groups, which form a gelled deposit in vivo without pH or temperature changes, allowing prolonged and controlled release of non-denatured active principles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If the native therapeutic protein is modified by covalent grafting of polymer chains or proteins, then the half-life in circulation increases and concentration variations are reduced, but the protein becomes irreversible modified leading to toxicity and immunogenicity problems
Solution Approach 1:
The patent introduces an intermediary carrier system (liposomes, microparticles, or colloidal suspensions) that temporarily holds the therapeutic protein and releases it gradually. This mediator approach allows prolonged circulation without chemically modifying the protein, thus extending half-life while avoiding the toxicity and immunogenicity associated with covalent grafting modifications.
Solution Approach 2:
The patent changes the physical state and delivery parameters of the therapeutic protein by formulating it in specialized carriers with controlled release properties. This physical parameter modification (encapsulation, controlled diffusion, gradual release) achieves prolonged duration of action without altering the protein's chemical structure, thereby preserving its safety profile.
2Reliability
If the therapeutic protein is administered repeatedly to maintain plasma concentration, then the therapeutic effect is sustained, but high concentration peaks cause pronounced harmful effects due to high toxicity
Solution Approach 1:
The patent implements periodic action through controlled release mechanisms in the carrier system. The therapeutic protein is released in gradual, sustained periods rather than acute peaks, maintaining therapeutic levels over time while avoiding the harmful concentration spikes that occur with repeated dosing. The release is controlled to be periodic and progressive, not pulsatile or explosive.
Solution Approach 2:
The patent ensures continuity of useful action by designing carrier systems that provide sustained, continuous release of the therapeutic protein. This eliminates the sawtooth concentration profile with its sharp peaks and troughs, replacing it with a flat, continuous release curve that maintains therapeutic levels without causing toxicity from peaks.
3Stability of the object's composition
If the formulation allows prolonged release of therapeutic protein, then plasma concentration variations are limited, but the formulation must meet strict specifications for liquid form, stability, and biocompatibility
Solution Approach 1:
The patent employs composite material systems combining therapeutic proteins with specialized carriers (liposomes, microparticles, colloidal suspensions). These composite formulations achieve stable plasma concentration profiles while meeting all required specifications for liquid form, sterility, stability, and biocompatibility through the synergistic properties of the composite structure.
Solution Approach 2:
The patent designs multi-functional carrier systems that simultaneously achieve prolonged release, maintain liquid form for easy injection, ensure stability during storage, and provide biocompatibility. These universal formulations satisfy multiple specification requirements (liquid form, sterility, stability, biocompatibility) through a single integrated system design, reducing the complexity of meeting individual requirements separately.
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 significantly prolonged release time of therapeutic proteins, reduces plasma concentration peaks, and maintains bioactivity, while being easy to inject and sterilize, with improved biocompatibility and local tolerance.
Implementation Method 1
forming a gelled deposit in vivo without pH or temperature changes
Implementation Method 2
submicronic particles of water-soluble biodegradable polymers with hydrophobic groups
Implementation Method 3
water-soluble biodegradable polymers
Data Source
AI summary
The present invention relates to novel pharmaceutical formulations based on stable, fluid aqueous colloidal suspensions for the prolonged release of active principle(s), particularly protein active principle(s), and to the applications, especially therapeutic applications, of these formulations.The object of the invention is to propose a fluid pharmaceutical formulation for the prolonged release of active principle(s) that makes it possible, after parenteral injection, to increase significantly the in vivo release time of a therapeutic protein while at the same time reducing the plasma concentration peak of the active protein, said formulation furthermore being stable on storage and also being biocompatible, biodegradable, non-toxic and non-immunogenic and having a good local tolerance.The formulation according to the invention is an aqueous colloidal suspension of low viscosity based on submicronic particles of water-soluble biodegradable polymer PO carrying hydrophobic groups (HG), said particles being non-covalently associated with at least one active principle (AP) and forming a gelled deposit at the injection site, this gelling being caused by a protein present in the physiological medium.