Organ transplantation is currently widely applied for organs such as heart, lung, pancreas, intestine (colon) and in particular kidney and liver. Increased organ demand and a shortage of donor organs has led to an increased waiting list for transplantation and a resulting interest in use of organs from sub-optimal donors.
Preservation of viability of donor organs is an important aspect in transplantation procedures. Organs to be transplanted obtained from cadavers must be stored and transported between hospitals and/or transplantation centers. Time is required for histo-compatibility testing of donor and recipient, and for the preparation of the receiving patient. Between retrieval from a donor and transplantation to a recipient, organs require special methods of preservation. The length of time that organs and tissues can be kept outside the body varies, depending on the organ, age and health of donor, the preservation method, preservation solution and temperature.
The standard clinical practice to date for preservation of most donor organs is hypothermic ischemic preservation. Organs are harvested from cadaveric donors after wash-out with a cold preservation solution. Thereby organs are exsanguinated and blood is replaced by a preservation solution which preferably mimicks physiological conditions. To replace blood and oxygen support of the organ and to maintain the organ in optimal condition, machine perfusion with a hypothermic preservation solution is sometimes applied for organs such as kidneys (WO 02/41696, U.S. Pat. No. 5,599,659 and U.S. Pat. No. 5,843,024). Machine perfusion allows the supply of compounds and oxygen to maintain organ viability, as well as removal of waste and toxic compounds, such as metabolites. Machine perfusion has shown to be superior to static preservation, although it has several possible drawbacks such as requirements for specialized equipment and trained personnel and additional requirements for the preservation solution applied.
The most commonly used solutions for donor organ preservation at hypothermic, static conditions are the University of Wisconsin solution (UW), in particular for liver and kidney (Janssen et al, Transplant International 2003, vol 16, no 7, p 515-522), Celsior for heart preservation and Euro-Collins or Perfadex for lung preservation. For machine perfusion, these have been modified to for instance UW-gluconate (Belzer MPS).
The current invention provides a new organ preservation solution, suitable for machine perfusion, for maintaining viability of organs, parts of organs and tissues. This solution has been designed to overcome a number of problems associated with hypothermic machine perfusion of donor organs, in particular organs obtained from sub-optimal donors, in particular non heart beating donors. The solution prevents or minimizes the adverse affects caused by ischemia, hypoxia, energy and nutrient depletion, acidification, hypothermia and reperfusion damage, which is experienced by organs to be used for transplantation purposes, and in particular by organs obtained from sub-optimal donors. The preservation solutions according to the current invention are superior to current state of the art preservation solutions, and are in particular advantageous for preservation and perfusion of organs obtained from sub-optimal donors, by supplying increased concentrations and an optimized balance of amino acids, vitamins, anti-oxidants, high molecular weight additives and enhanced buffering capacity. In addition, the preservation solution according to the invention combines optimal physical and chemical properties with the use of readily available, inexpensive and pharmaceutically tested and acceptable compounds, which reduces the cost of manufacturing and will facilitate medical certification of solutions according to the current invention.
USPTO Backgrounds
USPTO Backgrounds