L-Proline Viscosity Reduction in Immunoglobulin Preparations
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Solution Overview
Problem
Highly concentrated immunoglobulin (Ig) preparations for subcutaneous administration face challenges due to increased viscosity, leading to cumbersome handling and frequent administration at multiple sites, which can decrease patient acceptance and treatment efficacy.
Innovation Solution
The use of L-proline to reduce the viscosity of Ig preparations, allowing for higher concentrations while maintaining stability and enabling easier administration through its addition before the final concentration step, resulting in a preparation with a viscosity of less than 13 mPa·s for concentrations up to 20% Ig.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the concentration of immunoglobulin in the preparation is increased to reduce administration volume and frequency, then the viscosity of the preparation increases significantly, making handling cumbersome and administration difficult
Solution Approach 1:
L-proline is introduced as an intermediary substance that mediates between high immunoglobulin concentration and acceptable viscosity. The proline molecules interact with immunoglobulin molecules, preventing excessive aggregation and maintaining fluidity even at 20% Ig concentration, thus enabling both high concentration and ease of administration
Solution Approach 2:
The invention changes the chemical composition parameter of the preparation by adding L-proline, which fundamentally alters the viscosity-concentration relationship. This parameter change allows the system to achieve low viscosity at high immunoglobulin concentrations, resolving the contradiction between concentration and ease of operation
2Ease of operation
If L-proline is added to reduce viscosity and enable high concentration, then the preparation requires additional formulation steps and characterization, increasing process complexity
Solution Approach 1:
L-proline is added during the formulation process before final concentration, allowing it to prevent viscosity increase proactively rather than correcting it later. This preliminary action simplifies the overall process by preventing the problem rather than requiring complex correction steps
Solution Approach 2:
L-proline is used as a temporary, consumable formulation aid that performs its viscosity-reducing function and can be present in the final product at low levels. It is a simple, well-characterized amino acid that does not require complex recovery or removal processes
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 L-proline addition stabilizes Ig preparations, allowing for high-concentration, low-viscosity solutions that can be administered in smaller volumes quickly and simply, improving patient convenience and treatment acceptance by reducing the need for frequent injections and cumbersome handling.
Implementation Method 1
The use of L-proline to reduce the viscosity of Ig preparations, allowing for higher concentrations while maintaining stability
Implementation Method 2
the addition of basic or non-polar amino acids and the adjustment of the pH of the final preparation have been found to markedly decrease the formation of aggregates and thus increase the stability of those preparations
Data Source
AI summary
The present invention relates to the use of proline for reducing the viscosity of a protein preparation.