Methods of preparing pH-stabilized and heat-sterilized organ preservation and/or perfusion solutions
Inventors
Sigvardsson, Anne-Li • Sjöqvist, Elin
Assignees
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Publication Number
US-11849721-B2
Publication Date
2023-12-26
Expiration Date
Abstract
An organ preservation and/or perfusion solution for an isolated tissue or organ is provided. The solution comprises dextran, glucose, calcium ions, a buffer, and water, has a pH of 6.6 to 7.8, and is sterile based on having been subjected to heat sterilization. A method of preparing the solution also is provided. The method comprises combining dextran, glucose, calcium ions, buffer, and water to obtain an initial solution, adjusting the pH of the initial solution to 7.0 to 7.8 if needed, and subjecting the initial solution to heat sterilization, thereby obtaining the organ preservation and/or perfusion solution. A method of preserving and/or perfusing an isolated tissue or organ also is provided. A method for flushing, storage, and/or transportation of an isolated lung after removal from a donor in preparation for eventual transplantation into a recipient also is provided.
Core Innovation
The disclosed invention relates to pH-stabilized, heat-sterilized organ preservation and/or perfusion solutions for an isolated tissue or organ in a sterile container. The solutions include dextran, glucose, calcium ions, a buffer, and water, and are characterized by a pH of 6.6 to 7.8 at 25° C following heat sterilization. The solutions are provided as ready-to-use, pre-buffered and pre-calcium supplemented, so that further buffering and/or supplementation is not needed.
A stated rationale is that pre-buffering to a target pH range of about 7.0 to 7.8, together with calcium supplementation prior to heat sterilization, stabilizes glucose during autoclaving. This approach is described as synergistically reducing glucose degradation and reducing glucose degradation products generated during heat sterilization.
The document further describes that, with the stated formulations, measurable precipitate is not observed over storage. Embodiments are also described for lung flushing/storage/transportation, and the document reports glucose degradation and turbidity data, including nephelometric turbidity units, for TRIS buffered solutions with and without calcium.
Claims Coverage
The document includes two independent claims. Both claims cover preparing an organ preservation and/or perfusion solution in a sterile container by formulating an initial solution with specified components, adjusting pH at 25° C to a defined range, and heat sterilizing the container contents to achieve an F0 of at least 10.
Sterile-container heat-sterilized pH-defined organ preservation solution with TRIS buffer
A method of preparing an organ preservation and/or perfusion solution for an isolated tissue or organ in a sterile container, the organ preservation and/or perfusion solution having a pH of 6.6 to 7.8 at 25° C following heat sterilization, comprising preparing an initial solution comprising dextran, glucose at 0.5 to 5 g/L, calcium ions at 0.3 to 1.5 mM, and tris(hydroxymethyl)aminomethane (TRIS) buffer at 1 to 15 mM in water; adjusting the pH of the initial solution at 25° C to 7.0 to 7.8 if needed; and subjecting the initial solution in the container to heat sterilization at 115 to 130° C for at least 5 minutes to achieve an F0 of at least 10, thereby obtaining the organ preservation and/or perfusion solution in the sterile container.
Sterile-container heat-sterilized pH-defined organ preservation solution with TRIS buffer and phosphate
A method of preparing an organ preservation and/or perfusion solution for an isolated tissue or organ in a sterile container, the organ preservation and/or perfusion solution having a pH of 6.9 to 7.6 at 25° C following heat sterilization, comprising preparing an initial solution comprising dextran at 40 to 60 g/L, glucose at 0.5 to 5 g/L, calcium ions at 0.4 to 1 mM, tris(hydroxymethyl)aminomethane (TRIS) buffer at 2 to 5 mM, and phosphate in water; adjusting the pH of the initial solution at 25° C to 7.2 to 7.6 if needed; and subjecting the initial solution in the container to heat sterilization at 118 to 123° C for at least 10 minutes to achieve an F0 of at least 10, thereby obtaining the organ preservation and/or perfusion solution in the sterile container.
Across both independent claims, the core coverage is the preparation of a glucose-containing, calcium-containing, TRIS-buffered organ preservation and/or perfusion solution for an isolated tissue or organ in a sterile container, with pH adjusted at 25° C to a defined target range and heat sterilization performed in the container to reach an F0 of at least 10. One independent claim centers on TRIS buffer in the initial solution, while the other specifies TRIS buffer together with phosphate and narrower concentration and temperature ranges.
Stated Advantages
Stabilizes glucose during autoclaving and reduces glucose degradation products generated during heat sterilization.
No measurable precipitate is reported over storage.
Provides formulations suitable for lung flushing/storage/transportation.
Documented Applications
Lung flushing/storage/transportation using the disclosed organ preservation and/or perfusion solutions.
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