Arginine-Formulated Fibrinogen for Rapid Reconstitution
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Solution Overview
Problem
Current fibrinogen preparations, such as plasma cryoprecipitate, are time-consuming to dissolve and require aggressive mixing and vacuum sealing, leading to protein degradation, and pose logistic and transmissible risks, and existing logistic deficiencies, such as cold supply chains, short shelf-life, and the need for massive infusions due to significant protein loss during severe exsanguination.
Innovation Solution
A formulation comprising fibrinogen and arginine, which improves the solubility of solid fibrinogen compositions, allowing for fast dissolution within 20 minutes at atmospheric conditions and room temperature, without foaming or protein degradation, by using a specific concentration range of arginine that does not cause adverse effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If plasma cryoprecipitate is used for fibrinogen replacement, then fibrinogen can be supplied to treat hemorrhage, but it is time-consuming to dissolve and requires aggressive mixing that causes protein degradation
Solution Approach 1:
The patent changes the physical state parameter of fibrinogen from frozen (cryoprecipitate) to liquid form through viral inactivation and concentration processes. This parameter change eliminates the dissolution step entirely, reducing reconstitution time from over 20 minutes to immediate availability, while maintaining fibrinogen effectiveness for hemorrhage treatment
2Productivity
If aggressive mixing is used to dissolve cryoprecipitate, then dissolution speed increases, but protein degradation occurs
Solution Approach 1:
The patent extracts fibrinogen from the frozen cryoprecipitate matrix through viral inactivation and concentration processes, obtaining a liquid formulation that is already in dissolved state. This extraction eliminates the need for aggressive mixing, preventing protein degradation while maintaining high dissolution speed (immediate availability)
3Reliability
If frozen plasma cryoprecipitate is stored, then fibrinogen can be preserved, but cold supply chain and short shelf-life are required
Solution Approach 1:
The patent changes the storage temperature parameter from frozen (requiring cold supply chain) to refrigerated or ambient conditions through viral inactivation and formulation optimization. This parameter change eliminates the need for complex cold storage infrastructure while maintaining fibrinogen stability and extending shelf-life for hemorrhage treatment readiness
4Quantity of substance
If large volumes of FFP are transfused to provide fibrinogen, then fibrinogen supplementation is achieved, but transfusion-related complications increase
Solution Approach 1:
The patent extracts and concentrates fibrinogen from large volumes of plasma through centrifugation and filtration processes, creating a highly concentrated liquid formulation. This extraction reduces the required transfusion volume from large volumes of FFP to small volumes of concentrated fibrinogen solution, minimizing transfusion-related complications such as TRALI and viral transmission while maintaining adequate fibrinogen supplementation for hemorrhage treatment
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 formulation enables rapid reconstitution of fibrinogen, extending shelf life, simplifying supply chains, and facilitating accessible treatment in emergency cases of severe acute hemorrhages.
Implementation Method 1
A formulation comprising fibrinogen and arginine, which improves the solubility of solid fibrinogen compositions, allowing for fast dissolution within 20 minutes at atmospheric conditions and room temperature
Data Source
Figure 1A
Figure 1B
AI summary
Disclosed are compositions comprised of fibrinogen, Factor VIII, and a positively charged amino acid, wherein the ratio of the positively charged amino acid to Factor VIII ranges from above 1.4 to below about 8.3 mg/IU, respectively, the compositions being for use e.g., for intravenous administration. Further disclosed are methods for the preparation of the compositions.