Polyalkoxylated Nucleic Acid Separation via Precipitation
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Solution Overview
Problem
The production of polyalkoxylated nucleic acids is time and money consuming due to numerous steps of synthesis and purification, particularly in separating polyalkoxylated from non-polyalkoxylated nucleic acid molecules, which involves laborious and expensive chromatographic processes.
Innovation Solution
A method involving the precipitation of polyalkoxylated nucleic acid molecules from a mixture with non-polyalkoxylated molecules, allowing for the separation without prior chromatographic purification, and subsequent purification by HPLC and ultrafiltration, reducing the need for expensive resins and enhancing efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If chromatographic purification processes (RP-HPLC, IEX-HPLC) are used to separate polyalkoxylated from non-polyalkoxylated nucleic acid molecules, then purification efficiency is improved, but production time and cost increase significantly
Solution Approach 1:
The patent changes the physical-chemical parameters of the nucleic acid molecules by introducing polyalkoxylate moieties with specific molecular weights and charge densities. This creates distinct separation characteristics that enable efficient separation through precipitation and ultrafiltration rather than requiring complex chromatographic processes.
Solution Approach 2:
The patent extracts and removes the need for expensive and time-consuming chromatographic resins by using alternative separation mechanisms. The polyalkoxylated nucleic acids are separated from non-polyalkoxylated ones through precipitation and ultrafiltration, eliminating the requirement for RP-HPLC and IEX-HPLC purification steps.
2Manufacturing precision
If multiple purification steps (chromatography, ultrafiltration) are performed to remove truncated failure sequences, then product purity is improved, but manufacturing cost increases
Solution Approach 1:
The patent extracts and eliminates the need for expensive chromatographic resins by using precipitation and ultrafiltration as alternative purification methods. This reduces manufacturing costs while maintaining product purity through the removal of truncated failure sequences.
Solution Approach 2:
The patent replaces expensive, reusable chromatographic resins with cheaper, disposable ultrafiltration membranes and precipitation techniques. This substitution significantly reduces the cost of removing truncated failure sequences while achieving comparable or superior purity.
3Productivity
If several equivalents of polyalkoxylate-NHS are added in portions to increase yield, then reaction completeness is improved, but process complexity and time increase
Solution Approach 1:
The patent implements feedback control by monitoring the polyalkoxylation reaction progress and adjusting the addition of polyalkoxylate-NHS accordingly. This ensures complete reaction while avoiding unnecessary additions, thereby maintaining high yield without excessive process complexity.
Solution Approach 2:
The patent uses periodic addition of polyalkoxylate-NHS in controlled portions during the reaction process. This periodic action allows for complete conjugation while managing reaction time and complexity, achieving high yield through systematic progression rather than single large additions.
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 significantly simplifies the production process, reducing costs and time by efficiently separating polyalkoxylated nucleic acids from non-polyalkoxylated ones through precipitation, followed by effective purification, thereby improving the overall efficiency of polyalkoxylation.
Implementation Method 1
separating the polyalkoxylated nucleic acid molecule from a mixture of nucleic acid molecules... by precipitating the polyalkoxylated nucleic acid molecule from the mixture
Implementation Method 2
subsequent purification by HPLC and ultrafiltration
Implementation Method 3
subsequent purification by HPLC and ultrafiltration
Data Source
AI summary
A method of obtaining a polyalkoxylated nucleic acid, which can be used to make a modified drug, from a liquid mixture of polyalkoxylated and non-polyalkoxylated nucleic acids is described. The method involves use of a solvent or a mixture of solvents that allow the polyalkoxylated nucleic acids to precipitate out of the solution.