Cyclic Peptide Lung Perfusion for Ischemia Reperfusion Injury
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Solution Overview
Problem
Ischemia reperfusion injury remains a significant cause of early morbidity and mortality after lung transplantation, with current donor selection criteria being imprecise, leading to unrecognized injuries in donor lungs and limited availability of suitable organs for transplantation.
Innovation Solution
Extracorporeal lung treatment using a cyclized compound, such as those with specific amino acid sequences, is applied to perfuse and ventilate donor lungs ex vivo, improving ventilation performance and conditioning the lungs before transplantation by administering bio-active compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current donor selection criteria are used, then transplantation process is simple, but lung injury is unrecognized leading to graft failure
Solution Approach 1:
The patent applies preliminary action by performing ex vivo lung evaluation and treatment before transplantation. The donor lung is removed, perfused with therapeutic compounds, and assessed for function outside the body. This allows detection and treatment of injuries that would otherwise be unrecognized during standard intraoperative assessment, thereby improving measurement precision of lung injury detection without significantly increasing overall system complexity.
2Quantity of substance
If extended donor lungs are used, then organ availability increases, but early mortality and ICU stay increase
Solution Approach 1:
The patent applies parameter changes by modifying the physiological state of extended donor lungs through ex vivo perfusion with therapeutic compounds. The lung tissue is exposed to specific drugs, growth factors, or anti-inflammatory agents that alter biochemical parameters, reduce ischemia-reperfusion injury, and improve functional outcomes. This allows extended donor lungs to be salvaged and transplanted with success rates comparable to fresh donors, thereby increasing organ availability without compromising reliability.
3Quantity of substance
If donor lungs are rejected due to damage, then graft failure is prevented, but organ availability decreases
Solution Approach 1:
The patent applies the blessing in disguise principle by converting damaged donor lungs that would normally be rejected into viable transplant organs. Through ex vivo perfusion with therapeutic compounds, the damaged lung tissue is repaired, inflammation is reduced, and function is restored. Lungs that would have been discarded due to damage are thus salvaged and transplanted, converting a harmful situation into a beneficial outcome and significantly increasing the pool of usable donor lungs.
4Reliability
If ischemia reperfusion injury occurs, then early morbidity and mortality increase, but treatment options are limited
Solution Approach 1:
The patent applies preliminary anti-action by administering therapeutic compounds during ex vivo lung perfusion before transplantation to prevent ischemia-reperfusion injury. Anti-inflammatory drugs, antioxidants, and other protective agents are delivered directly to the lung tissue in advance, creating a protective effect that prevents the harmful inflammatory cascade that would otherwise occur upon reperfusion after transplantation. This preliminary protective action significantly improves post-transplant survival by preventing the development of severe ischemia-reperfusion injury.
Data Source
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Figure 2A~2B
AI summary
A method of conditioning/improving lung functions extracorporeally by treatment of a lung ex vivo with a cyclized compound of the amino acid sequence of formula I: X1-GQRETPEGAEAKPWY-X2 wherein X1 comprises an amino acid (sequence) with 1 to 4 members, comprising natural or unnatural amino acids, and X2 comprises one amino acid, selected from natural amino acids; and a pharmaceutical composition, comprising a peptide of formula I as defined in any one of claims 1 to 7, in in a form, which is appropriate for spraying to obtain an aerosol for inhalation, or which is appropriate for the preparation of a spray to obtain an aerosol upon spraying, which is appropriate for inhalation.