Crystalline Forms of Compound 1 for Angiogenic Disease Treatment
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Solution Overview
Problem
Current treatments for diseases associated with aberrant signaling of growth factors and 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 D, which are prepared through mixing with methanol or water, and their use in pharmaceutical compositions to treat proliferative diseases by inhibiting abnormal angiogenesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If crystalline forms of Compound 1 are developed for therapeutic use, then therapeutic efficacy for treating angiogenic diseases is improved, but manufacturing and characterization complexity increases
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions (solvent type, temperature, pH) to generate distinct crystalline forms with different properties. Each crystalline form (A through G) represents a specific parameter set that optimizes therapeutic efficacy while providing identifiable characterization patterns for quality control.
Solution Approach 2:
The patent segments the compound's solid-state forms into distinct crystalline polymorphs, each with unique diffraction patterns and stability profiles. This segmentation allows selection of specific crystalline forms optimized for different therapeutic applications and manufacturing requirements, resolving the contradiction between efficacy and manufacturability.
2Adaptability or versatility
If multiple crystalline forms are characterized and prepared, then therapeutic options and optimization possibilities increase, but process complexity and time requirements increase
Solution Approach 1:
The patent performs preliminary action by pre-characterizing multiple crystalline forms and establishing their preparation methods in advance. This allows the therapeutic community to select from pre-validated options without needing to perform extensive characterization work, thereby reducing overall process time while maintaining versatility.
Solution Approach 2:
The patent utilizes phase transitions during crystallization to generate different crystalline forms from the same compound. By controlling transition conditions (solvent, temperature, pH), multiple stable phases are accessible through relatively simple process modifications, increasing therapeutic options without proportionally increasing process complexity.
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 effectively treat diseases like cancer, macular degeneration, and diabetic retinopathy by inhibiting aberrant angiogenesis, providing a therapeutic solution for conditions associated with pathological growth factor signaling.
Implementation Method 1
Some embodiments include a process for preparing a crystalline form E described herein, comprising mixing Compound 1 and methanol. Some embodiments include a process for preparing a crystalline form D described herein, comprising mixing Compound 1 and water at room temperature or at 40° C.
Implementation Method 2
Some embodiments include a process for preparing a crystalline form E described herein, comprising mixing Compound 1 and methanol. Some embodiments include a process for preparing a crystalline form D described herein, comprising mixing Compound 1 and water at room temperature or at 40° C.
Implementation Method 3
the crystalline form has an X-ray powder diffraction (XRPD) pattern with a largest peak at about 10-11 degrees 2θ. Some embodiments include, a crystalline form of Compound 1 having an X-ray powder diffraction (XRPD) pattern with a largest peak at about 18-19 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.