Polymer based transplant preservation solution

Abstract

Provided are transplant preservation solutions comprising a polyglycerol wherein the polyglycerol is of a molecular weight between about 0.15 kDa and about 3.99 kDa, methods and uses thereof as well as kits providing said transplant preservation solutions.

1 . A transplant preservation solution comprising a polyglycerol wherein the polyglycerol is of a molecular weight between about 0.15 kDa and about 3.99 kDa. 
     
     
         2 . A transplant preservation solution comprising an UW-type organ preservation solution and a polyglycerol wherein the polyglycerol is of a molecular weight between about 0.15 kDa and about 3.99 kDa. 
     
     
         3 . The transplant preservation solution of  claim 1  wherein the polyglycerol is of a molecular weight between about 0.48 kDa and about 3.0 kDa. 
     
     
         4 . The transplant preservation solution of  claim 1  wherein the pH of the transplant preservation solution is between about 2.0 and about 9.0. 
     
     
         5 . The transplant preservation solution of  claim 1  wherein the pH of the transplant preservation solution is between about 6.5 and about 7.5. 
     
     
         6 . The transplant preservation solution of  claim 1  wherein the transplant preservation solution is in aqueous solution. 
     
     
         7 . The transplant preservation solution of  claim 6  wherein the polyglycerol comprises about 0.01% by weight to about 50% by weight of the transplant preservation solution. 
     
     
         8 . The transplant preservation solution of claim wherein the polyglycerol comprises about 1.25% by weight to about 20% by weight of the transplant preservation solution. 
     
     
         9 . The transplant preservation solution of  claim 1  wherein the transplant preservation solution has an osmolarity between about 150 milliosmols per litre and about 1500 milliosmols per litre. 
     
     
         10 . The transplant preservation solution of  claim 1  wherein the polyglycerol has a polydispersity of about 1.0 to about 15. 
     
     
         11 . The transplant preservation solution of  claim 1  wherein the polyglycerol is dendritic. 
     
     
         12 . The transplant preservation solution of  claim 1  wherein the degree of branching of the polyglycerol is between about 0 and about 0.4. 
     
     
         13 . The transplant preservation solution of  claim 1  wherein the degree of branching of the polyglycerol is between about 0.4 and about 0.7. 
     
     
         14 . The transplant preservation solution of  claim 1  wherein the degree of branching of the polyglycerol is between about 0.7 and about 1.0. 
     
     
         15 . The transplant preservation solution of  claim 1  wherein the degree of branching of the polyglycerol is zero. 
     
     
         16 . The transplant preservation solution of  claim 1  comprising at least two polyglycerols wherein the molecular weight of each of the at least two polyglycerols is different. 
     
     
         17 . The transplant preservation solution of  claim 1  wherein the polyglycerol further comprises one or more hydrophobic groups, hydrophilic groups or both. 
     
     
         18 . The transplant preservation solution of  claim 17  wherein the one or more hydrophobic groups, hydrophilic groups or both are joined to from about 1% to about 100% of hydroxyl groups on the polyglycerol. 
     
     
         19 . The transplant preservation solution of  claim 17  wherein the one or more hydrophobic groups, hydrophilic groups or both are joined to from about 1% to about 40% of hydroxyl groups on the polyglycerol. 
     
     
         20 . The transplant preservation solution of  claim 17  wherein the one or more hydrophobic groups, hydrophilic groups or both comprise one or more of a carboxylic acid, an amine, a substituted amine, a quaternary amine, an amino acid, a phosphate, a sulfate, a sulfonate, a phosphonate, an alkyl, an alkene, an alkyne, an alkyl ether, an aromatic, an aromatic ether, a zwitterionic group, a carbohydrate, a disulfide, a ketal, a substituted ketal, an acetal, a substituted acetal, ester groups, thioesters, a urethane, ester-amides, amide groups, a peptide, a phenol, halogens, or a thiol. 
     
     
         21 . The transplant preservation solution of  claim 1  further comprising at least one of the group consisting of: one or more electrolytes; one or more xanthine oxidase inhibitors; one or more antioxidants; one or more nucleosides; one or more amino acids; one or more diffusion agents; one or more osmotic agents; one or more growth factors; one or more buffering agents; and one or more anti-cell death agents. 
     
     
         22 .- 30 . (canceled) 
     
     
         31 . The transplant preservation solution of  claim 21  wherein the osmotic agent or diffusion agent is selected from at least one of the group consisting of: sodium, chloride, bicarbonate, a bicarbonate producing agent, sulfate, phosphate, calcium, potassium, magnesium, lactobionate, dextrose, fructose, glycerol, sorbitol, manitol, L-carnitine, bovine serum albumin (BSA), maltose, maltotriose, maltopentose, xylitol, adenosine, glutathione, lactobionic acid, potassium hydroxide, synthetic polymers, and natural polymers. 
     
     
         32 . The transplant preservation solution of  claim 21  wherein the transplant preservation solution comprises an osmotic agent and the osmotic agent comprises lactobionate. 
     
     
         33 . The transplant preservation solution of  claim 21  wherein the transplant preservation solution comprises a buffering agent and the buffering agent is selected from at least one of the group consisting of: maleic acid, phosphoric acid, sulfate, citric acid, malic acid, formic acid, lactic acid, succinic acid, acetic acid, pivalic acid, pyridine, piperazine, picolinic acid, L-histidine, 3-(N-morpholino)propanesulfonic acid (MOPS), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), tricine, glycyglycine, bicine, boric acid, and glycine. 
     
     
         34 . The transplant preservation solution of  claim 1  wherein the polyglycerol comprises a hyperbranched polyglycerol. 
     
     
         35 . The transplant preservation solution of  claim 1  wherein the polyglycerol comprises a linear polyglycerol. 
     
     
         36 .- 42 . (canceled) 
     
     
         43 . A method of treating a patient in need of an organ transplant or in need of a tissue transplant or in need of a cell transplant, the method comprising administering the transplant preservation solution of  claim 1  to a donor organ or a donor tissue or a donor cell, transporting the donor organ or the donor tissue or the donor cell, and transplanting the donor organ or the donor tissue or the donor cell. 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 43  wherein the transplant preservation solution is administered more than once per day. 
     
     
         47 . A kit for formulating a transplant preservation solution, the kit comprising:
 (a) a lyophilized polyglycerol wherein the polyglycerol is of a molecular weight between about 0.15 kDa and about 3.99 kDa; and   (b) instructions for using the lyophilized polyglycerol for formulating the transplant preservation solution.   
     
     
         48 . The kit of  claim 47  wherein the kit is for formulating an UW-type transplant preservation solution. 
     
     
         49 . The kit of  claim 47  wherein the polyglycerol is of a molecular weight between about 0.48 kDa and about 3.0 kDa. 
     
     
         50 . The kit of  claim 47  further comprising at least one of the group consisting of: one or more electrolytes; one or more amino acids; one or more xanthine oxidase inhibitor; one or more antioxidants; one or more nucleosides; one or more growth factors; one or more buffering agents; one or more anti-cell death agents; one or more diffusion agents; and one or more osmotic agents. 
     
     
         51 .- 59 . (canceled) 
     
     
         60 . The kit of  claim 50  wherein the kit comprises at least one osmotic agent or comprises at least one diffusion agent and the at least one osmotic agent or diffusion agent is selected from at least one of the group consisting of: sodium, chloride, bicarbonate, a bicarbonate producing agent, sulfate, phosphate, calcium, potassium, magnesium, lactobionate, dextrose, fructose, glycerol, sorbitol, manitol, L-carnitine, bovine serum albumin (BSA), maltose, maltotriose, maltopentose, xylitol, adenosine, glutathione, lactobionic acid, potassium hydroxide, synthetic polymers, and natural polymers. 
     
     
         61 . The kit of  claim 50  wherein the kit comprises an osmotic agent and the osmotic agent comprises lactobionate. 
     
     
         62 . The kit of claim  56  wherein the buffering agent is selected from at least one of the group consisting of: maleic acid, phosphoric acid, sulfate, citric acid, malic acid, formic acid, lactic acid, succinic acid, acetic acid, pivalic acid, pyridine, piperazine, picolinic acid, L-histidine, 3-(N-morpholino)propanesulfonic acid (MOPS), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), tricine, glycyglycine, bicine, boric acid, and glycine. 
     
     
         63 . A composition comprising the transplant preservation solution of  claim 1  and at least one physiologically acceptable salt, buffer, diluent or excipient, for use as an transplant preservation solution. 
     
     
         64 . The composition of  claim 63  wherein the composition is in aqueous solution. 
     
     
         65 . The composition of  claim 64  wherein the composition is a lyophilized product.