Tri-block copolymer controlled release drug depots
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Solution Overview
Problem
Current controlled release systems for water-soluble drugs, such as those used in difficult-to-dose areas like the eyes, joints, and spine, often experience burst release, which is not suitable for drugs requiring a linear dosage profile, and lack compatibility with radiopaque markers for imaging.
Innovation Solution
A tri-block copolymer composition comprising a poly-(ethylene glycol) block and a poly(lactide-co-ε-caprolactone) block, with acylated hydroxyl end-groups and a block ratio between 1.4 and 2.6, combined with a pharmaceutically active ingredient and radiopaque atoms for controlled release and imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional thermogel systems are used for controlled release, then the drug can be delivered to difficult-to-dose areas, but burst release occurs which is not suitable for drugs requiring linear dosage profiles
Solution Approach 1:
The patent modifies the polymer composition parameters by incorporating specific ratios of hydrophilic blocks (PEG) and hydrophobic blocks (PLA-PCL), along with controlling molecular weight and hydroxyl end-group content, to achieve controlled release kinetics that prevent burst release while maintaining ease of injection into difficult-to-dose areas
Solution Approach 2:
The invention uses composite block copolymer structures combining hydrophilic PEG blocks with hydrophobic PLA-PCL blocks in specific ratios, creating a material that exhibits both gelation properties for localized delivery and controlled degradation for sustained release, thereby resolving the contradiction between ease of dosing and dosage profile control
2Productivity
If conventional thermogel systems are used, then controlled release can be achieved, but the systems lack compatibility with radiopaque markers for imaging
Solution Approach 1:
The patent creates a multi-functional polymer system that simultaneously provides controlled drug release, radiopacity for imaging, and biodegradability, allowing the same material to serve both therapeutic and diagnostic purposes without compromising either function
Solution Approach 2:
The invention introduces radiopaque atoms or molecules as intermediaries that can be incorporated into or associated with the block copolymer structure, enabling imaging visibility while maintaining the controlled release properties of the polymer matrix
3Stability of the object's composition
If the polymer forms a gel at body temperature for controlled release, then the drug depot is stabilized, but the gel may be affected by shear forces during injection and movement
Solution Approach 1:
The patent optimizes the molecular weight, block ratios, and hydroxyl end-group content of the polymer to fine-tune the gelation temperature and rheological properties, ensuring the gel forms stable drug depots at body temperature while maintaining sufficient flowability and shear resistance during injection and physiological movement
Solution Approach 2:
The invention creates local structural heterogeneity within the gel matrix through the block copolymer architecture, where hydrophilic and hydrophobic domains are distributed at different scales, providing both stable gelation at the molecular level and mechanical resilience to shear forces at the macro level
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 provides a controlled release of water-soluble drugs with reduced burst release and prolonged release profiles, maintaining integrity under mild shear forces, and allows for radiopaque marking for imaging, enhancing treatment success and imaging visibility.
Implementation Method 1
the polymer is soluble in the solvent used at room temperature (e.g. 21 °C) and forms a gel once injected into the body (temperature in the range from 30 to 42°C)
Implementation Method 2
the composition provides a controlled release of water-soluble drugs with reduced burst release and prolonged release profiles
Data Source
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AI summary
The invention describes a special class of drug-depot forming triblock copolymers which are very suitable for the loading, containment and releasing of sensitive drugs such as proteins from biodegradable, injectable drug depots. Furthermore the invention describes how to visualize these depots for various imaging related purposes. The invention relates to a composition comprising a tri-block copolymer according to formula 1 B-A-B (1), wherein A stands for a linear poly-(ethylene glycol) block and wherein B stands for wherein B stands for a poly(lactide-co-ε-caprolactone) block, wherein the hydroxyl end-groups of the tri-block copolymer are at least partially acylated with an optionally substituted acyl having 2 to 12 C-atoms, C-atoms of the substituents included;an active ingredient, preferably a pharmaceutically active ingredient and a solvent, wherein the block ratio of the tri-block copolymer, which ratio is defined as the ratio between the sum of the average molecular weight of the B- blocks and the sum of the average molecular weight of the A-block ranges from 1.4 to 3.5. This composition is suitable for controlled release of a pharmaceutically active ingredient.