Blood storage container containing aqueous composition for the storage of red blood cells
Inventors
Assignees
Publication Number
US-11730676-B2
Publication Date
2023-08-22
Expiration Date
2033-08-22
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Abstract
A blood storage container along with an aqueous composition for the storage of packed red blood cells is described. In a preferred embodiment, the container is not made of DEHP plasticizer. In some embodiments, the container is made from a polymeric material and a non-DEHP plasticizer. In some embodiments, the aqueous composition is made of about 1 to about 3 mM adenine, about 20 to about 115 mM dextrose, about 15 to about 60 unmetabolizable membrane-protectant sugar, about 20 to about 30 mM sodium bicarbonate, and about 4 to about 20 mM disodium phosphate. In a most preferred embodiment, the DEHP-lacking container is made from a PVC polymeric material and a DINCH plasticizer and the aqueous composition is made of about 2 mM adenine, about 80 mM dextrose, 55 mM unmetabolizable membrane-protectant sugar, about 26 mM sodium bicarbonate, and about 12 mM disodium phosphate.
Core Innovation
The invention provides a combination product comprising a blood storage container and an aqueous composition for the storage and preservation of red blood cells (RBCs). The core feature is the use of a container lacking DEHP (di-ethyhexyl phthalate) plasticizer, typically made from a polymeric material such as polyvinyl chloride (PVC) combined with a non-DEHP plasticizer, including but not limited to DINCH or other non-phthalate plasticizers. The container is paired with a specifically formulated aqueous composition designed to support RBC storage under standard blood banking procedures at refrigeration temperatures (about 1 to 6° C.), without requiring periodic mixing.
The aqueous composition consists essentially of adenine (about 1 to about 3 mM), dextrose (about 20 to about 115 mM), at least one non-metabolizable membrane-protectant sugar (such as mannitol, about 15 to about 60 mM), a physiologically acceptable sodium salt (typically sodium bicarbonate, about 20 to about 130 mM), and a phosphate source (such as disodium phosphate, about 4 to about 20 mM), with the composition being substantially free of exogenously derived chloride ions and, in some embodiments, citrate. The pH buffering system present in the composition is formulated to maintain a pH in the stored RBC suspension that favors glycolysis over synthesis of 2,3-diphosphoglycerate (DPG), thereby increasing adenosine triphosphate (ATP) yield and supporting cell viability over prolonged storage.
This invention addresses the critical problem of storing red blood cells in containers free of DEHP plasticizer, which is being phased out due to toxicity concerns. While alternative plasticizers are available, they lack the unintentional but beneficial RBC-preserving effects that DEHP provided, resulting in regulatory performance issues (such as excess hemolysis) with existing storage solutions. The present invention overcomes this problem by combining specific container and solution chemistries that jointly maintain RBC integrity, viability, and physiologic function within regulatory hemolysis standards for at least 42 days, and potentially longer, under standard blood banking conditions.
Claims Coverage
The patent defines three main independent inventive features, each focused on the combination of a DEHP-lacking container and a specific aqueous storage composition for red blood cells.
DEHP-lacking container for red blood cell storage
A container for storing red blood cells that lacks DEHP plasticizer, comprising at least a portion of a wall made of polyvinyl chloride (PVC) polymeric material combined with a non-phthalate plasticizer such as DINCH, BTHC, DENT, or TEHTM.
Aqueous storage composition with defined components and buffering system
An aqueous composition to be contained within the container, comprising: - Adenine (about 1–3 mM) - Dextrose (about 20–115 mM) - Disodium phosphate (about 4–15 mM) - At least one non-metabolizable membrane-protectant sugar (about 15–60 mM, including mannitol) - A physiologically acceptable sodium salt (about 20–130 mM, such as sodium bicarbonate) - A pH buffering system of physiologically acceptable agents providing bicarbonate anions, phosphate anions, and sodium cations - Substantially free of exogenously derived chloride ions and, in some embodiments, citrate - Osmolarity between about 210 and 340 mOsmoles/liter - Maintains pH to establish and maintain an intracellular reaction equilibrium that favors glycolysis over synthesis of 2,3-DPG from 1,3-DPG during the storage period, resulting in net ATP gain.
Combination product enabling RBC storage under regulatory standards without periodic mixing
A combination product as described, enabling storage of red blood cells at about 1 to 6° C. without periodic mixing under standard blood banking procedures, where the product supports meeting U.S. regulatory standards for hemolysis (below 1.0% with 95% confidence and reliability for at least 42 days) when using the defined non-DEHP container and aqueous composition.
In summary, the claims cover the combination of a DEHP-lacking RBC storage container and a specifically formulated, chloride-free (and optionally citrate-free) aqueous composition with defined concentrations and buffering chemistry, enabling extended RBC storage with maintained viability and compliance to regulatory hemolysis standards, without the need for periodic mixing.
Stated Advantages
Facilitates prolonged storage of red blood cells within regulatory hemolysis limits (below 1.0% hemolysis for at least 42 days) even in the absence of DEHP plasticizer.
Supports RBC integrity and physiological function, including maintenance of ATP levels and cell morphology, when stored under standard conditions in a non-DEHP container.
Eliminates the need for periodic mixing of stored red blood cells, enabling compatibility with standard blood banking procedures.
Avoids toxicity concerns associated with DEHP by using alternative non-phthalate plasticizers, such as DINCH, in the blood storage container.
Maintains RBC viability and quality after prolonged storage, expecting improved performance upon transfusion compared to conventional solutions in non-DEHP containers.
Documented Applications
Storage and preservation of collected red blood cells for later transfusion into patients, including trauma, post-chemotherapy, surgery, or treatment of blood-borne diseases such as anemias.
Use in standard blood bank processing and storage procedures for packed red blood cells, including leukoreduced and non-leukoreduced units.
Storage of red blood cells prepared via apheresis, collected whole blood, or separated into components by filtration or centrifugation.
Direct infusion of stored red blood cell suspensions in the described additive solution into patients in need of transfusion.
Rehydration of lyophilized (freeze-dried) RBCs or thawing of stored frozen blood or pathogen-inactivated RBC products.
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