Virus-Inactivated Thrombin via Solvent-Detergent and Anion Exchange
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Solution Overview
Problem
Current methods for preparing thrombin often involve the use of animal-derived products like thromboplastin, which can be sources of infectious viruses and contaminants, and do not effectively inactivate both enveloped and non-enveloped viruses, posing risks in clinical applications.
Innovation Solution
A process involving solvent-detergent virus inactivation of prothrombin and factor X, followed by loading onto an anion exchange medium, washing, and activating with metal ions to form thrombin, which allows for the removal of contaminants and viruses without the need for thromboplastin and achieves multiple virus inactivation steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If animal-derived thromboplastin is used to activate prothrombin, then the activation reaction proceeds effectively, but the risk of viral contamination and undesirable side effects increases
Solution Approach 1:
The invention extracts and removes the harmful animal-derived thromboplastin component from the activation process. Instead of using external animal-derived thromboplastin, the patent utilizes endogenous prothrombin activator present in the plasma fraction itself, thereby eliminating the source of viral contamination while maintaining effective prothrombin activation
Solution Approach 2:
The patent employs a single-use plasma fraction containing prothrombin and endogenous activator, eliminating the need for reusable or stored animal-derived thromboplastin products that could serve as viral reservoirs. Each batch is freshly prepared and used immediately, preventing viral persistence
2Object-affected harmful factors
If solvent-detergent treatment is applied to PPSB starting material, then enveloped viruses are inactivated, but other necessary factors such as phospholipids are eliminated
Solution Approach 1:
The patent performs solvent-detergent treatment at an earlier stage in the purification process, before the final thrombin formulation is prepared. This preliminary inactivation step removes enveloped viruses from the starting plasma or plasma fraction, while subsequent purification steps restore or supplement necessary phospholipids and other factors needed for thrombin activation and stability
Solution Approach 2:
The invention introduces phospholipid supplements or phospholipid-containing carriers as intermediary substances to replace the phospholipids removed during solvent-detergent treatment. These intermediary phospholipid sources provide the necessary cofactors for prothrombin activation without reintroducing viral contamination risks
3Reliability
If multiple virus inactivation steps are implemented, then the safety against different virus types increases, but the process complexity and production time increase
Solution Approach 1:
The patent employs a multi-functional plasma fraction that contains not only prothrombin but also endogenous prothrombin activator and other necessary co factors. This single concentrated plasma fraction serves multiple functions: it provides the substrate for thrombin generation, contains built-in activation capability, and can be subjected to comprehensive virus inactivation treatments, thereby simplifying the overall process while maintaining safety
Solution Approach 2:
The invention merges multiple purification and concentration steps into a single integrated process using the PPSB fraction. By combining prothrombin concentration, activator preservation, and virus inactivation into a unified workflow, the patent reduces the number of separate operations while achieving comprehensive virus inactivation and high thrombin yield
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 results in highly purified and concentrated thrombin, minimizing contamination risks and enabling effective inactivation of both enveloped and non-enveloped viruses, thereby enhancing the safety and purity of thrombin for clinical use.
Implementation Method 1
loading the product of step (a) onto an anion exchange medium
Implementation Method 2
activating the prothrombin on the medium to form thrombin by the addition of metal ions
Implementation Method 3
solvent-detergent virus inactivation of a solution comprising prothrombin and factor X
Data Source
AI summary
The present invention relates to processes for the preparation of virus inactivated thrombin, and to the products prepared by these processes.