Preservation solutions

Abstract

There is described a preservation solution for the preservation of cells, tissues and/or organs, said solution comprising: (i) water for injection; (ii) at least one saccharide; (iii) at least one component with pH buffer properties; (iv) optionally at least one component with calcium transport blocking properties or an anti-calcium action activity; (v) salicylic acid, in free form or in salt form, or aspirin; and (vi) glutamic acid, in free form or in salt form, or glutamine; provided that acetamide is absent and/or if aspirin is present glutamine is absent and if glutamine is present aspirin is absent.

1 . A preservation solution for the preservation of cells, tissues and/or organs, in the absence of a blood supply, said solution comprising:
 (i) water for injection;   (ii) at least one saccharide;   (iii) at least one component with pH buffer properties;   (iv) optionally at least one component with calcium transport blocking properties or an anti-calcium action activity;   (v) salicylic acid, in free form or in salt form, or aspirin; and   (vi) glutamic acid, in free form or in salt form, or glutamine;   provided that acetamide is absent and/or if aspirin is present glutamine is absent and if glutamine is present aspirin is absent, such that acetamide is not formed;   wherein the solution is a flush preservation solution and/or a cold storage preservation solution.   
     
     
         2 . A preservation solution according to  claim 1  wherein if (v) is aspirin, (vi) is glutamic acid, in free form or in salt form. 
     
     
         3 . A preservation solution according to  claim 1  wherein if (vi) is glutamine, (v) is salicylic acid, in free form or in salt form. 
     
     
         4 - 6 . (canceled) 
     
     
         7 . A preservation solution according to  claim 1  wherein (v) is salicylic acid, in free form or in salt form; and (vi) is glutamic acid, in free form or salt form, or glutamine; and aspirin is absent, such that acetic acid and/or acetamide are not formed. 
     
     
         8 . (canceled) 
     
     
         9 . A preservation solution according to  claim 1  wherein (v) is salicylic acid, in free form or in salt form, or aspirin; and (vi) is glutamic acid, in free form or salt form; and glutamine is absent, such that ammonia and/or acetamide are not formed. 
     
     
         10 . A preservation solution according to  claim 1  wherein aspirin and glutamine are absent. 
     
     
         11 - 14 . (canceled) 
     
     
         15 . A preservation solution according to  claim 1  wherein the amount of salicylic acid, in free form or in salt form, is less than 0.5 mmol/L. 
     
     
         16 . (canceled) 
     
     
         17 . A preservation solution according to  claim 9  wherein aspirin, if present, is in an amount of from about 0.3 mmol/L to about 1.0 mmol/L. 
     
     
         18 . A preservation solution according to  claim 1  wherein the amount of glutamic acid, in free form or in salt form, present is less than 20 mmol/L. 
     
     
         19 . (canceled) 
     
     
         20 . A preservation solution according to  claim 1  wherein glutamine, if present, is in an amount of from about 15 mmol/L to about 30 mmol/L. 
     
     
         21 . A preservation solution according to  claim 1  wherein the saccharide is selected from one or more of from sucrose, raffinose and mannitol. 
     
     
         22 . A preservation solution according to  claim 21  wherein the saccharide is sucrose. 
     
     
         23 . A preservation solution according to  claim 1  wherein the pH buffer is selected from a sodium phosphate buffer, a potassium phosphate buffer and the like such as, Na 2 HPO 4 , NaH 2 PO 4 , K 2 HPO 4 , KH 2 PO 4  and the like; and combinations thereof. 
     
     
         24 . (canceled) 
     
     
         25 . A preservation solution according to  claim 1  wherein the calcium transport blocker or anti-calcium activity agent is selected from any known calcium transport or channel blocker, such as one or more of nicardipine, diltiazem, verapamil, nisoldipine, chlorpromazine or trifluorperazine. 
     
     
         26 . (canceled) 
     
     
         27 . A preservation solution according to  claim 1  wherein the preservation solution includes at least one anion that is largely impermeable into cells. 
     
     
         28 . A preservation solution according to  claim 27  wherein the anion that is largely impermeable into cells is an impermeant sequestering anion, such as lactobionate or lactobionic acid. 
     
     
         29 . (canceled) 
     
     
         30 . A preservation solution according to  claim 1  wherein the preservation solution includes at least one component with colloid osmotic properties, such as polyethylene glycol (PEG), succinylated gelatin (as in Gelofusine), Ficoll (a polysaccharide) or a starch product. 
     
     
         31 . (canceled) 
     
     
         32 . A preservation solution according to  claim 1  wherein the preservation solution includes an inorganic or organic solute, such as an electrolyte including cations and/or anions, for example selected from Na + , K + , Cl − , OH −  and the like; and combinations thereof. 
     
     
         33 - 34 . (canceled) 
     
     
         35 . A preservation solution according to  claim 1  wherein the preservation solution includes at least one component with calcium chelating properties. 
     
     
         36 - 40 . (canceled) 
     
     
         41 . A preservation solution according to  claim 1  wherein the preservation solution includes at least one component that is effective against oxygen free radicals or the production of oxygen free radicals, such as allopurinol and reduced glutathione, or a combination thereof. 
     
     
         42 - 56 . (canceled) 
     
     
         57 . A preservation solution according to  claim 1  wherein the solution has a pH in the range 6.5-7.8. 
     
     
         58 - 67 . (canceled) 
     
     
         68 . A method for the preservation of cells for simple hypothermic storage, in particular living cells, tissues or organs whereby the cells, tissue or organs are brought into contact with a preservation solution comprising:
 (i) water for injection;   (ii) at least one saccharide;   (iii) at least one component with pH buffer properties;   (iv) optionally at least one component with calcium transport blocking properties or an anti-calcium action activity;   (v) salicylic acid, in free form or in salt form, or aspirin; and   (vi) glutamic acid, in free form or in salt form, or glutamine;   provided that acetamide is absent and/or if aspirin is present glutamine is absent and if glutamine is present aspirin is absent;   whereby the cells, tissue or organ are flushed with solution, removed from the normal locus, cooled to temperatures normally in the range between zero and 12° C. and stored.   
     
     
         69 - 100 . (canceled) 
     
     
         101 . A preservation solution for the preservation of cells, tissues and/or organs, in the absence of a blood supply, said solution comprising:
 (i) water for injection;   (ii) at least one saccharide;   (iii) at least one component with pH buffer properties;   (iv) optionally at least one component with calcium transport blocking properties or an anti-calcium action activity;   (v) salicylic acid, in free form or in salt form, and/or aspirin; and   (vi) glutamic acid, in free form or in salt form, and/or glutamine;   provided that if aspirin is present glutamine is absent and if glutamine is present aspirin is absent and/or wherein if aspirin and/or acetamide and/or acetic acid is present, the amount of salicylic acid present exceeds that which can be attributed to degradation from aspirin, for example as determined by the sum of the amounts of any acetic acid and of any acetamide present; and/or   wherein if glutamine and/or acetamide and/or ammonia is present, the amount of glutamic acid present exceeds that which can be attributed to degradation from glutamine, for example as determined by the sum of the amounts of any ammonia and of any acetamide present.   
     
     
         102 . (canceled) 
     
     
         103 . A preservation solution for the preservation of cells, tissues and/or organs, in the absence of a blood supply, said solution comprising:
 (i) water for injection;   (ii) sucrose;   (iii) Na 2 HPO 4  and NaH 2 PO 4 ;   (iv) diltiazem;   (v) salicylic acid, in free form or in salt form, or aspirin; and   (vi) glutamic acid, in free form or in salt form, or glutamine,   provided that acetamide is absent and/or if aspirin is present glutamine is absent and if glutamine is present aspirin is absent, such that acetamide is not formed;   together with lactobionic acid, KOH and NaOH, glutathione and allopurinol and PEG, and any optional additional components;   whereby the cells, tissue or organ are flushed with solution, removed from the normal locus, cooled to temperatures normally in the range between zero and 12° C. and stored.