Lung Preservation Composition with Dextran Buffer
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Solution Overview
Problem
Current lung preservation solutions fail to effectively extend the preservation time of donor lungs beyond 6-8 hours at cold temperatures, leading to ischemia-reperfusion injury and cellular damage, with limited ability to test multiple variants due to reliance on animal models.
Innovation Solution
Development of a non-carbonic buffered nutrient media containing amino acids, vitamins, and dextran, optionally with prostaglandin E1, alpha 1 antitrypsin, and other cytoprotective agents, tested using cell culture models to improve lung preservation and reduce ischemia-reperfusion injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If traditional preservation solutions (Collins, UW, LPDG) are used, then electrolyte balance is maintained, but preservation time is limited to 6-8 hours and cellular damage occurs
Solution Approach 1:
The patent changes the fundamental parameters of preservation solutions by replacing traditional inorganic salt-based formulations with a non-carbonic buffered nutrient media containing amino acids, vitamins, and dextran. This parameter change enables extended preservation beyond 6-8 hours while reducing cellular damage, as the nutrient-rich composition supports cellular metabolism during prolonged storage.
Solution Approach 2:
The invention creates a composite preservation solution by combining multiple functional components: non-carbonic buffer systems (phosphate, Tris, HEPES), amino acids (glutamine, arginine), vitamins, dextran, and cytoprotective agents. This composite formulation synergistically addresses both preservation time extension and cellular damage reduction.
2Reliability
If animal models are used to test preservation solutions, then physiological relevance is achieved, but testing multiple variants and time points is impractical and requires many animals
Solution Approach 1:
The patent creates simplified in vitro copies of lung tissue using cell culture models that replicate key physiological responses to preservation. These cell culture systems serve as surrogate models that maintain physiological relevance while enabling high-throughput testing of multiple solution variants and time points without requiring numerous animal subjects.
3Use of energy by moving object
If cold temperature storage (4°C) is used, then metabolic rate is reduced, but cell damage is induced and preservation time is limited
Solution Approach 1:
The patent converts the harmful effect of cold-induced cellular stress into a beneficial outcome by formulating preservation solutions containing cytoprotective agents and nutrients that specifically counteract cold temperature damage. The non-carbonic buffered nutrient media with amino acids and vitamins actively protects cells from cold-induced apoptosis and necrosis, transforming the inherently damaging cold storage condition into a safe and effective preservation method.
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 solution significantly improves lung preservation by reducing cell death, alveolar wall swelling, and apoptosis, extending preservation time and maintaining lung viability, as demonstrated in rat and pig lung transplant models.
Implementation Method 1
a non-carbonic buffered nutrient media, the non-carbonic buffered nutrient media comprising at least one amino acid and at least one vitamin
Implementation Method 2
a dextran and optionally prostaglandin E1 (PGE1)
Data Source
AI summary
Provided is a lung preservation composition comprising a non-carbonic buffered nutrient media, preferably a phosphate buffered nutrient media, and a dextran, optionally Dextran 40 and and optionally prostaglandin E1 (PGE1), and optionally at least one of alpha 1 antitrypsin (A1AT), an impermeant, optionally raffinose, an antioxidant, optionally glutathione, and necrostatin-1. Also described is a method of preserving a lung prior to and/or during transplant using said lung preservation composition, and kits comprising one or more components of the lung preservation composition.