Lyophilized Thrombin Composition with Saccharide Excipients
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Solution Overview
Problem
Current methods for lyophilizing thrombin solutions result in long processing times, high water content, and low thrombin activity recovery upon reconstitution, leading to increased costs and reduced stability of the solid thrombin compositions.
Innovation Solution
A method involving an aqueous thrombin solution with specific compositions, including 1-4.6% saccharides or sugar alcohols, 0.7-1.75% sodium chloride, 0.2-3% albumin, calcium chloride, and sodium acetate, which is lyophilized using a shorter cycle involving controlled freezing, primary, and secondary drying procedures to produce a stable and highly active solid thrombin composition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional lyophilization methods are used for thrombin solutions, then the solid thrombin composition can be produced, but the processing time is long and thrombin activity recovery is low
Solution Approach 1:
The patent modifies the chemical composition parameters of the thrombin solution by adding specific excipients (mannitol at 2-10%, sucrose at 2-10%, HSA at 0.1-5%, and surfactants at 0.001-0.05%) to change the physical and chemical properties of the solution, enabling faster lyophilization while preserving thrombin activity
Solution Approach 2:
The patent introduces intermediary substances (excipients such as mannitol, sucrose, HSA, and surfactants) that mediate between the thrombin protein and the lyophilization process, protecting thrombin from denaturation and facilitating faster drying while maintaining activity recovery
2Quantity of substance
If conventional lyophilization methods are used, then solid thrombin composition is produced, but the water content remains high
Solution Approach 1:
The patent changes the formulation parameters by incorporating specific concentrations of excipients that modify the freezing and drying characteristics of the solution, enabling rapid removal of water while achieving low final water content (<3%) in the solid composition
3Reliability
If stabilizers and cryoprotectants are added to protect thrombin, then protein stability is improved, but the formulation complexity increases
Solution Approach 1:
The patent employs excipients that perform multiple functions simultaneously: mannitol and sucrose act as both cryoprotectants and bulking agents, HSA provides both stabilization and bulk, and surfactants prevent aggregation while maintaining solubility, thereby reducing formulation complexity through multi-functional components
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 reduces lyophilization time by 37%, achieves a low water content, and maintains high thrombin activity recovery upon reconstitution, ensuring stability and cost-effectiveness of the solid thrombin compositions.
Implementation Method 1
lyophilization typically refers to the process of freezing a mixture and then reducing the concentration of water e.g. by sublimation
Implementation Method 2
reducing the concentration of water e.g. by sublimation to levels which do not support biological or chemical reactions
Data Source
AI summary
Provided are methods for lyophilization of an aqueous thrombin solution, thrombin solutions for use in such lyophilization methods, and solid thrombin compositions produced by such methods.