Indocyanine Green Purification via Continuous Soxhlet Extraction
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Solution Overview
Problem
Conventional methods for purifying indocyanine green are complex, expensive, and inefficient, especially at an industrial scale, due to the difficulty in removing sodium iodide impurities, which limits the diagnostic use and increases production costs.
Innovation Solution
A method utilizing solubility differences between impurities and betaines, specifically employing continuous Soxhlet extraction with anhydrous solvents like methylene chloride to separate indocyanine green from sodium iodide, allowing for efficient removal of insoluble impurities like NaI while leaving the dye soluble in the solvent.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional purification methods are used to remove sodium iodide, then purification can be achieved, but the process becomes complex and expensive, significantly increasing production costs
Solution Approach 1:
The patent applies extraction principle by using a solvent system to selectively extract and remove sodium iodide from the indocyanine green product. The method uses a specific solvent mixture that dissolves sodium iodide while leaving the dye behind, enabling simple removal of the impurity through a single extraction step rather than complex purification procedures
Solution Approach 2:
The patent changes the solubility parameters by selecting a specific solvent system with appropriate polarity and dielectric constant. By adjusting the solvent composition and properties, the method creates conditions where sodium iodide becomes soluble while indocyanine green remains insoluble, enabling selective removal through parameter optimization rather than complex processing
2Manufacturing precision
If conventional purification methods are used, then some purification can be achieved, but the process is time-consuming and inefficient, especially at industrial scale
Solution Approach 1:
The patent implements continuous extraction where the solvent continuously contacts the solid indocyanine green product, dissolving sodium iodide and removing it from the system. This continuous process eliminates the need for repeated batch operations, significantly reducing processing time and increasing productivity while maintaining high purification efficiency
Solution Approach 2:
The method uses the natural solubility differences between sodium iodide and indocyanine green in the selected solvent system to achieve automatic separation. The impurity self-extracts from the product without requiring external intervention, complex equipment, or multiple processing steps, enabling rapid and efficient purification at industrial scale
3Ease of manufacture
If sodium iodide is used as precipitating reagent in synthesis, then the dye can be produced, but sodium iodide remains as impurity in the product, limiting diagnostic use
Solution Approach 1:
The patent applies extraction to remove the harmful impurity (sodium iodide) from the synthesized product. By using a selective solvent system, the method extracts sodium iodide from the indocyanine green product, enabling the dye to meet purity requirements for diagnostic use while maintaining the simplicity of the conventional synthesis route
Solution Approach 2:
The patent introduces a solvent system as an intermediary medium that facilitates the removal of sodium iodide. This intermediary substance selectively interacts with the impurity, dissolving it and enabling separation from the product through simple filtration or decantation, thus bridging the gap between easy synthesis and high purity requirements
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 process significantly reduces sodium iodide content to below the tolerance range for parenteral use, enabling effective large-scale purification of indocyanine green without altering the conventional synthesis route, thereby enhancing its diagnostic utility and reducing production costs.
Implementation Method 1
The extraction is carried out in an organic, preferably anhydrous, solvent, in particular in an aprotic solvent (e.g. CH 2 Cl 2 or ethyl acetate). The possibility of removing Nal from indocyanine green or separating it from it by extraction is surprising insofar as indocyanine green is only moderately soluble in the anhydrous solvent CH 2 Cl 2 preferably used, whereas Nal is insoluble.
Implementation Method 2
The anhydrous solvents can be dried in a manner known per se using molecular sieves, P 2 O 5 , etc.
Implementation Method 3
The extraction is therefore preferably carried out continuously. The so-called Soxhlet extraction is particularly suitable for this purpose. For continuous extraction, the material to be purified is preferably placed in a sleeve or similar receiving device which is permeable to the solvent and continuously flushed with solvent just below its boiling point.
Implementation Method 4
The deep green solution obtained was then concentrated on a rotary evaporator and lyophilized.
Implementation Method 5
The deep green solution obtained was then concentrated on a rotary evaporator and lyophilized.
Data Source
AI summary
The invention relates to a method for purification of synthetically-produced compounds, comprising a betaine structure in the molecule, for example, indocyan green, characterised in that reaction by-products, starting materials and/or other impurities such as Nal used during production are separated by extraction.