1. Field of the Invention
The present invention relates to a composition for organ preservation comprising an inulin type fructan and a method for preserving an organ using the same.
2. Related Art
Organ transplantation can be adopted as last therapy in the case where commonly used therapy cannot be effectively carried out without difficulties because of severe organ diseases such as end-stage organ failure.
For example, in Japan, “The Law on Organ Transplantation (the so-called the Organ Transplant Law)” was enforced on October, 1997, and, in addition to conventionally approved organ transplantation from a living donor (particularly liver transplantation from a living donor), organ transplantation from a brain death donor has become legally possible. On the other hand, in Europe and United States, an organ donation system was already established at least 30 years ago, and up to now, there are not less than 40,000 cases for heart transplant and several hundreds of thousands of cases for kidney transplant. In Europe and United States, medical transplantation has become ubiquitous in society as a form of medical treatment.
The reason why transplantation therapy has become considered as one of safe therapies is that necessary environment is being in place, that is, for example, transplants can be satisfactorily secured, organ preservation techniques have been improved, transplantation techniques have been improved, and the control of rejection is possible. What is important in organ transplantation is not only to successfully enucleate an organ from a donor (an organ donor) and to successfully transplant the organ into a recipient (a donor recipient), but also to preserve the organ harvested from the donor in a good state. In general, when blood flow in organs in a living body is stopped for a long period of time, they are necrotized. For example, it is said that, when the liver is in an ischemic state for 30 to 90 min at room temperature, an irreversible change occurs. In the case of organ transplantation from a living donor, the amount of time between the enucleation of the organ and the transplantation can be regulated. On the other hand, in the case of organ transplantation from a brain death donor in which facilities where organ transplantation is carried out are different from facilities where the organ is harvested, there is a limitation on a reduction in the amount of time between the enucleation of the organ and the transplantation of the organ, because a lot of time is often taken for the selection of a recipient due to histocompatibility and the like and the transport of the organ and the like. One of important points, which have a decisive influence on whether or not organ transplantation can be conducted with successful results, is to preserve the harvested organ for the longest possible period of time while maintaining the structure and function of the organ.
The harvested organ is generally preserved by a low-temperature immersion method. In this method, initial perfusion (flushing) in which the harvested organ is washed with a cooled perfusate is conducted, and the organ is then subjected to low-temperature immersion preservation using a cooled preserving solution. The oxygen consumption can be suppressed by cooling the organ. When the organ is preserved in a cooled state, however, a sodium pump of cell membrane is broken. For this reason, the use, as a solution for organ preservation, of a solution having the same composition as a high-potassium/low-sodium intracellular fluid has been regarded as advantageous.
At first, for example, Collins solution containing glucose and an intracellular fluid-type electrolyte, and Euro-collins solution having the same composition as the Collins solution except for the absence of magnesium were used as the organ preservative. These preserving solutions are effective for the kidney, but on the other hand, the effect of protecting tissues and cells in organs other than the kidney is sometimes unsatisfactory.
In recent years, UW (University of Wisconsin) solution developed by a research group in University of Wisconsin has in many cases become used as an organ preservative. This UW solution can prolong preservation time of the liver and the pancreas and is disclosed, for example, in Japanese Patent Publication No. 68082/1995 (U.S. Pat. No. 4,879,283, German Patent No. 3843958) and Japanese Patent Publication No. 22801/1996. The UW solution is an electrolytic solution containing lactobionate and raffinose as an impermeation agent, hydroxyethyl starch as a colloid osmo-regulator, and adenosine or insulin as an energy metabolism promoting component. The is UW solution is commercially available from DuPont Pharmaceuticals under the tradename designation ViaSpan and is extensively used clinically. The UW solution, however, suffers from problems of stability and preparation methods. Further, since the UW solution is a preserving solution in a single commodity form, in some cases, it cannot be said that the UW solution can satisfactorily cope with various organs such as heart, liver, kidney, lung, pancreas, and small intestine.
Thus, there remains a need for an organ preservative which can alleviate the problem posed by the preservation of the organ, can improve the state of preservation of the organ, and can prolong the preservation time.
The organ preservative generally contains sugars such as glucose, raffinose, and mannitol. So far as the present inventors know, however, there is substantially no finding on what type of sugars is proper for organ preservation.
For example, Japanese Patent Laid-Open Publication No. 40801/1994 (Europe Patent Publication No. 0580444) discloses an organ preservative comprising trehalose, hydroxyethyl starch, and various electrolytes. This publication, however, does not disclose the applicability of inulin type fructans.
USPTO Backgrounds
USPTO Backgrounds