Liquid medium for infusion and preservation of organs.

0001The invention relates to a liquid medium for infusion in and preservation of solid organs, such as kidneys, pancreas, livers, hearts and others, being particularly appropriate for infusion in kidney blood vessels and subsequent preservation of kidneys.

0002As is known, prior to performing a transplant, the organ is removed from the body of the donor. Where the organ is a kidney, it is preserved in an appropriate medium while the future recipient is being prepared. Finally, the organ is implanted in the recipient.

0003To preserve an organ, particularly in the case of kidneys, the kidney blood vessels are infused at the time of removal. As is generally known, infusion means the artificial circulation in the organ of a liquid medium having a composition appropriate for maintaining the functions of the organ. During the infusion, the liquid medium entrains the blood contained in the blood vessels, particularly the vessels for microcirculation, thereby avoiding the formation of microclots which would occlude the renal capillaries and would make the organ useless for transplant. This operation lasts for about 10 to 15 minutes.

0004The infused organ is then stored in a sterile container at a temperature of about 4^oC such as to be submerged in a liquid having the same composition as the infusing liquid.

0005The purpose of infusion and the subsequent cold storage is not only to make the organ viable for transplant, but furthermore to get the organ to work immediately it is transplanted. The aim, in the case of kidneys, is to avoid the post-transplant renal insufficiency which, regrettably, is still very frequent in human kidney transplants. Post-transplant oliguric renal insufficiency causes difficulties for the clinical management of the patient, obliges the use of dialysis while the oliguria lasts and makes kidney transplants more expensive, at the same time as there is a poorer prognosis for the functional survival of the graft.

0006Currently, the liquid infusion medium regularly used in kidney transplant units is a solution proposed by Dr Collins, called "Eurocollins', the ionic composition of which imitates that of the intracellular medium and glucose is used to provide it with an osmolarity similar to that of the intra and extracellular medium.

0007Nevertheless, the "Eurocollins" liquid medium has the drawback that the glucose diffuses through the cellular membranes, causing intracellular oedema, which is one of the most important factors in the onset of the post-­transplant renal insufficiency.

0008To avoid the above drawback, the present invention proposes a liquid medium characterised in that it includes an amount of mannitol lying between 3.4 and 4.6 wt%, preferably between 4.0 and 4.4 wt%.

0009In a preferred development of the invention, further to the said amount of mannitol, the liquid medium comprises also an amount of sodium allopurinol lying between 0.025 and 0.1 wt%.

0010As is known. mannitol is a hexatomic alcohol having the formula CH₂OH-(CHOH)₄-CH₂OH.

0011The advantage of mannitol over glucose is that it does not diffuse through the cellular membrane, i.e., it is a good impermeabilising agent, whereby it maintains the tonicity of the extracellular medium and prevents the intracellular oedema mentioned above.

0012Furthermore, mannitol is a potent scavenger of hydroxyl type free oxygen radicals.

0013In turn, allopurinol is a potent inhibitor of the enzyme xanthinooxidase, whereby the degradation of the renal uric acid and, therefore, the production of the free oxygen radicals responsable for renal damage during the reinfusion of the organ with blood, particularly if the cold ischaemia exceeds 16 hours duration, is avoided.

0014Consequently, the liquid medium containing mannitol but not including sodium allopurinol is useful in common clinical practice with regular cold ischaemia times, while the medium containing sodium allopurinol is used preferably with extended cold ischaemia periods.

0015One example of a composition according to a centesimal formula of the medium of the invention is as follows: <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="center"><u style="single">COMPOSITION 1</u></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Mannitol....</entry><entry namest="col2" nameend="col2" align="char" char=".">4.19 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Monopotassium phosphate....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.205 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Dipotassium phosphate...</entry><entry namest="col2" nameend="col2" align="char" char=".">0.907 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Potassium chloride....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.112 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Sodium bicarbonate....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.084 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Water, q.s. ad....</entry><entry namest="col2" nameend="col2" align="char" char=".">100 ml</entry></row></tbody></tgroup></table></tables>

0016And an example of a composition, according to a cen­tesimal formula, of a medium according to the invention containing sodium allopurinol is the following: <tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><thead valign="top"><row><entry namest="col1" nameend="col2" align="center"><u style="single">COMPOSITION 2</u></entry></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Mannitol....</entry><entry namest="col2" nameend="col2" align="char" char=".">4.19 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Monopotassium phosphate....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.205 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Dipotassium phosphate...</entry><entry namest="col2" nameend="col2" align="char" char=".">0.907 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Potassium chloride....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.112 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Sodium bicarbonate....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.084 g</entry></row><row><entry namest="col1" nameend="col1" align="left">Sodium allopurinol....</entry><entry namest="col2" nameend="col2" align="char" char=".">0.05 g</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Water, q.s. ad....</entry><entry namest="col2" nameend="col2" align="char" char=".">100 ml</entry></row></tbody></tgroup></table></tables>

0017With these two new infusion media, no case of oliguric renal insufficiency has been observed in twenty recipients of a kidney from a donor corpse, 10 of the kidneys having been infused with composition 1 and a further 10 with composition 2.

0018It is noted that the invention does not consist of a method of surgical or therapeutical treatment of the human or animal body, since the medium according to the invention has no properties to cure patients.

0019It is also noted that the medium according to the invention is not a chemical product, since it is obtained physically, by way of mixtures and solutions.