Crystalline Forms of Compound 1 for Angiogenic Ocular Disease Treatment
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Solution Overview
Problem
Current treatments for diseases associated with aberrant angiogenesis, such as cancer and macular degeneration, lack effective therapeutic compositions that can inhibit pathological angiogenesis.
Innovation Solution
The development of crystalline forms of Compound 1, specifically crystalline forms E and F, which are prepared through methods involving methanol and water-isopropanol crystallization, offering potential therapeutic benefits for treating angiogenic ocular diseases by administering a therapeutically effective amount.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new therapeutic compositions are developed to inhibit pathological angiogenesis, then treatment effectiveness for diseases like cancer and macular degeneration is improved, but the complexity of drug formulation and crystalline structure characterization increases
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing different crystalline forms (polymorphs) of Compound 1, each with distinct X-ray powder diffraction patterns. Crystalline form E shows a largest peak at 10-11 degrees 2θ, while crystalline form F shows a largest peak at 17-18 degrees 2θ. These parameter changes in molecular arrangement lead to improved therapeutic reliability for inhibiting pathological angiogenesis in diseases like cancer and macular degeneration.
Solution Approach 2:
The patent utilizes phase transitions by preparing different crystalline forms through specific crystallization processes. Crystalline form E is prepared by mixing Compound 1 with methanol, while crystalline form F is prepared by crystallizing Compound 1 in water and isopropanol. These phase transition processes from solution to solid crystalline state enable the formation of distinct polymorphic forms with different therapeutic properties.
2Adaptability or versatility
If multiple crystalline forms are prepared through different crystallization methods, then therapeutic options and efficacy are improved, but the manufacturing process complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the manufacturing process into distinct pathways for producing different crystalline forms. One pathway involves mixing Compound 1 with methanol to produce crystalline form E, while another pathway involves crystallizing Compound 1 in water and isopropanol to produce crystalline form F. This segmentation allows selective production of specific crystalline forms based on therapeutic needs, improving adaptability while maintaining manageable manufacturing complexity through standardized procedures.
Solution Approach 2:
The patent uses intermediary substances (solvents) to mediate the formation of different crystalline forms. Methanol serves as an intermediary in producing crystalline form E, while water and isopropanol serve as intermediaries in producing crystalline form F. These intermediary solvents facilitate the phase transition from solution to crystalline solid, enabling controlled formation of specific polymorphic forms with distinct therapeutic properties.
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 crystalline forms of Compound 1 provide a promising treatment for diseases related to aberrant angiogenesis, including cancer and macular degeneration, by effectively inhibiting abnormal angiogenesis, thereby addressing the need for new therapeutic compositions in this area.
Implementation Method 1
a process for preparing a crystalline form E described herein, comprising mixing Compound 1 and methanol
Implementation Method 2
a process for preparing a crystalline form F described herein, comprising crystallizing Compound 1 in water and isopropanol
Implementation Method 3
the crystalline form has an X-ray powder diffraction (XRPD) pattern with a largest peak at about 10-11 degrees 2θ
Implementation Method 4
an X-ray powder diffraction (XRPD) pattern with a largest peak at about 17-18 degrees 2θ
Data Source
AI summary
Described herein are crystalline forms of Compound 1 useful for the prevention and treatment of angiogenic ocular conditions; methods of treating a disease comprising; processes for preparing; and kits comprising, the same.