OXY133 Polymorph Crystallization for Bone Growth
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Solution Overview
Problem
There is a need for developing different polymorphic forms of OXY133 and a robust, reproducible process for the production of OXY133 monohydrate to enhance its osteogenic properties for medical applications such as bone growth promotion.
Innovation Solution
The process involves converting OXY133 into polymorph Form A or monohydrate through specific solvent and anti-solvent ratios at controlled temperatures, using solvents like isopropanol, tetrahydrofuran, and acetone with water, and optimizing conditions for crystallization to achieve desired X-ray powder diffraction patterns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional bone grafting methods are used, then bone growth can be promoted, but the procedure is invasive and requires taking bone from the patient's own body
Solution Approach 1:
The patent extracts the essential osteogenic function from autogenous bone grafts by isolating and purifying oxysterol compounds (specifically 20(S)-hydroxycholesterol and OXY133) that naturally promote bone growth. This extraction allows the active bone-growing component to be separated from the need for invasive bone harvesting procedures.
Solution Approach 2:
The patent employs synthetic oxysterol compounds that can be produced through chemical synthesis rather than requiring biological sourcing. These synthetic molecules provide the necessary osteogenic activity without needing to be derived from donor bone tissue, eliminating the invasive harvesting process while maintaining bone growth promotion capabilities.
2Reliability
If rhBMP-2 is used to promote spine fusion, then bone growth is enhanced, but the cost and complexity of the procedure increase significantly
Solution Approach 1:
The patent replaces complex recombinant protein therapy (rhBMP-2) with simpler synthetic oxysterol compounds. These small molecule compounds can be synthesized through established chemical processes, avoiding the need for complex biotechnology manufacturing, purification, and storage requirements associated with recombinant proteins.
Solution Approach 2:
The patent changes the chemical parameter space from large recombinant proteins to small synthetic oxysterol molecules. This parameter change simplifies the overall treatment approach, as oxysterols have better stability, easier synthesis, and simpler formulation requirements compared to recombinant BMP-2 protein.
3Reliability
If multiple polymorphic forms of OXY133 are developed, then the osteogenic properties can be optimized, but the manufacturing process becomes more complex
Solution Approach 1:
The patent systematically varies crystallization parameters (solvent type, temperature, pH, concentration) to generate different polymorphic forms of OXY133. Each polymorph is characterized by its unique X-ray diffraction pattern and is selected based on its specific osteogenic performance, stability, and manufacturability characteristics.
Solution Approach 2:
The patent exploits phase transition phenomena during crystallization to generate different polymorphic forms of OXY133. By controlling the crystallization conditions, the patent directs the formation of specific crystal phases (polymorphs) that exhibit enhanced osteogenic properties, improved stability, or better manufacturability.
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
This method produces OXY133 monohydrate with a yield of 85% to 94% and allows for the creation of various pharmaceutical compositions, providing a scalable and efficient route to enhance bone growth applications.
Implementation Method 1
precipitating the OXY133 polymorph by adding an anti-solvent at a temperature sufficient to precipitate the OXY133 polymorph
Implementation Method 2
precipitating the OXY133 monohydrate by adding water to the mixture
Implementation Method 3
subjecting a slurry of OXY133 to conditions sufficient to convert OXY133 to OXY133 monohydrate or polymorph Form A
Data Source
AI summary
Compositions and methods for preparing OXY133 polymorphs Form C to Form I are provided. The methods include subjecting a slurry of OXY133 to conditions sufficient to convert OXY133 to the OXY133 polymorph Form C, polymorph Form D, polymorph Form E, polymorph Form F, polymorph Form G, polymorph Form H, polymorph Form I or a mixture thereof. A polymorph of OXY133 is also provided and that polymorph can be polymorph Form C, polymorph Form D, polymorph Form E, polymorph Form F, polymorph Form G, polymorph Form H, polymorph Form I or a mixture thereof. Pharmaceutical compositions including OXY133 polymorphs are also provided.