Nucleic Acid Formulations With Excipients for Viscosity Reduction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
High viscosity of nucleic acid solutions, particularly at concentrations above 1, 3, or 5 mg/ml, complicates parenteral administration, manufacturing processes, and increases processing times and costs, leading to potential nucleic acid destabilization and loss.
Innovation Solution
Incorporation of excipients such as arginine, phenylalanine, ornithine, meglumine, benzenesulfonic acid, pyridoxine, and thiamine phosphoric acid ester into nucleic acid solutions to reduce viscosity and stabilize the nucleic acids, utilizing synergistic combinations to enhance effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If nucleic acid concentration is increased to achieve high therapeutic dose in small injection volume, then dosage efficiency is improved, but viscosity increases making injection difficult
Solution Approach 1:
The patent introduces viscosity-reducing excipients (mediators) such as arginine, phenylalanine, ornithine, meglumine, benzenesulfonic acid, pyridoxine, and thiamine phosphoric acid ester into the nucleic acid formulation. These excipients act as intermediaries that interact with the nucleic acid molecules to reduce intermolecular interactions and lower solution viscosity, thereby enabling injection of highly concentrated formulations without compromising dosage efficiency
Solution Approach 2:
The patent changes the chemical composition parameters of the formulation by adding specific excipients at optimized concentrations. This parameter change (adding viscosity-reducing agents) transforms the physical properties of the nucleic acid solution, reducing its viscosity while maintaining the required high concentration for therapeutic efficacy
2Productivity
If nucleic acid concentration is increased to reduce manufacturing volume and processing time, then productivity is improved, but handling and processing becomes difficult
Solution Approach 1:
The excipients serve as mediators during manufacturing processes, facilitating easier handling of concentrated nucleic acid solutions. They reduce viscosity throughout the manufacturing workflow, enabling standard equipment to process high-concentration formulations efficiently
3Quantity of substance
If high concentration formulations are used to reduce injection volume, then patient compliance is improved, but shear stress increases causing nucleic acid destabilization
Solution Approach 1:
The patent applies prior cushioning by incorporating viscosity-reducing excipients and stabilizing agents into the formulation before administration. These additives cushion the nucleic acid molecules against shear stress during injection, preventing destabilization while enabling the use of high concentrations for reduced injection volume
Solution Approach 2:
The excipients act as protective intermediaries between the nucleic acid and the mechanical stress of injection. They form a protective environment that reduces shear stress impact on the nucleic acid structure, maintaining stability even at high concentrations
Data Source
AI summary
The present invention relates to liquid compositions comprising a nucleic acid having a reduced viscosity. Furthermore, the invention relates to methods for reducing the viscosity of a liquid compositions comprising a nucleic acid.