Peptide Crystal B Preparation via Solvent and Temperature Control
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Solution Overview
Problem
The existing methods for crystallizing the cyclohexapeptide compound are time-consuming, low-yielding, and unsuitable for industrial production, with most solvents being ineffective except for aqueous propanol, which is not suitable for high-purity crystal formation.
Innovation Solution
A method involving dissolving the compound in an aqueous organic solvent and reducing the temperature, or adding a low-polarity solvent, to precipitate a novel crystal form with specific X-ray diffraction and differential scanning calorimetry patterns, using solvents like methanol, ethanol, and ethyl acetate to achieve high yield and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If aqueous propanol is used as crystallizing solvent, then crystal can be obtained, but the method is time-consuming (12-20 hrs) and low-yielding (85.2% at the most)
Solution Approach 1:
The patent changes the crystallization parameters by using different solvent systems (aqueous ethanol, aqueous isopropanol, or acetone) and adjusting temperature parameters to achieve faster crystallization with higher yield, resolving the contradiction between purity and productivity
Solution Approach 2:
The patent utilizes phase transition of the compound from dissolved state to crystalline state by controlling temperature reduction and solvent addition, enabling efficient crystal formation that overcomes the time-consuming nature of conventional crystallization
2Manufacturing precision
If aqueous propanol is used as crystallizing solvent, then crystal can be obtained, but the method is unsuitable for industrial production
Solution Approach 1:
The patent modifies the crystallization parameters by substituting propanol with industrially more suitable solvents (ethanol, isopropanol, or acetone) while maintaining crystal purity, making the process suitable for industrial production
Solution Approach 2:
The patent employs readily available, inexpensive solvents that are easy to handle and dispose of in industrial settings, replacing the less suitable aqueous propanol system with more practical solvent options
3Adaptability or versatility
If the compound of formula I is used directly, then it can serve as therapeutic or intermediate, but it is hard to crystallize and generally amorphous
Solution Approach 1:
The patent induces phase transition from amorphous to crystalline state through controlled crystallization processes using specific solvent systems and temperature reduction, enabling the compound to form stable crystals suitable for storage and further processing
Solution Approach 2:
The patent uses specific solvents (aqueous ethanol, aqueous isopropanol, or acetone) as intermediaries to facilitate crystal formation from the amorphous compound, enabling controlled crystallization that preserves the compound's 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 method results in a high-yielding, high-purity crystal form with specific characteristics, suitable for industrial production and downstream synthesis, improving the purity and stability of the compound.
Implementation Method 1
dissolving the compound of formula I in an aqueous organic solvent (i) to form solution a
Implementation Method 2
obtaining crystal B of the peptide substance by reducing the temperature of solution a
Implementation Method 3
reducing the temperature of solution a
Implementation Method 4
adding another low polarity solvent (ii) into solution a
Implementation Method 5
crystal B has peaks at the following 2θ angles in the X-ray diffraction pattern (XRPD)
Implementation Method 6
crystal B has the maximum peak at 155-165° C. in the differential scanning calorimetry pattern (DSC)
Data Source
AI summary
The present invention discloses a crystal of a peptide substance and the preparation method as well as the use thereof. Said crystal B possesses peaks at the following 2θ angles in the X-ray diffraction pattern (XRPD): 3.2±0.2°, 5.4±0.2°, 6.2±0.2°, and 9.3±0.2°.