Platelet additive solution having a beta-galactosidase inhibitor

1. A platelet additive solution (PAS) for storing platelets having a platelet surface, wherein active endogenous sialidase and β-galactosidase migrate to the platelet surface during storage, wherein sialic acid loss and galactose loss are reduced on the platelet surface of isolated platelets during storage, wherein the isolated platelets are obtained from one or more donors, the PAS comprises:

a. about 0.1 mM to about 100 mM of one or more β-galactosidase inhibitors and about 0.1 mM to about 100 mM of one or more sialidase inhibitors, and optionally an amount of one or more glycan-modifying agents, or a combination thereof; and

b. PAS components that includes a salt, a phosphate source, a citrate source, a carbon source, an acetate source, or any combination thereof;

wherein when combined with platelets to thereby obtain a platelet composition, cleavage by endogenous sialidase and β-galactosidase of sialic acid or galactose, respectively, is reduced, as compared to isolated platelets not subjected to the PAS and wherein once the platelet composition is transfused into one or more recipients, circulation time of platelets is increased, platelet clearance is reduced, or both, as compared to circulation time of platelets, platelet clearance, or both in one or more recipients that have not been subjected to PAS.

2. The PAS of claim 1 , wherein the one or more sialidase inhibitors is selected from the group consisting of: fetuin; 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA); ethyl (3R,4R,5S)-5-amino-4-acetamido-3-(pentan-3-yloxy)-cyclohex-1-ene-1-carboxylate); (2R,3R,4S)-4-guanidino-3-(prop-1-en-2-ylamino)-2-((1R,2R)-1,2,3-trihydroxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid; (4S,5R,6R)-5-acetamido-4-carbamimidamido-6-[(1R,2R)-3-hydroxy-2-methoxypropyl]-5,6-dihydro-4H-pyran-2-carboxylic acid; (1S,2S,3S,4R)-3-[(1S)-1-acetamido-2-ethyl-butyl]-4-(diaminomethylideneamino)-2-hydroxy-cyclopentane-1-carboxylic acid; a combination thereof; and a pharmaceutically acceptable salt thereof.

3. The PAS of claim 1 , wherein the sialidase inhibitor is the sodium salt of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid.

4. The PAS of claim 1 , wherein the one or more β-galactosidase inhibitors is selected from the group consisting of: 1-deoxygalactonojirimycin (DGJ); N-(n-butyl)deoxygalactonojirimycin; N-(n-nonyl)deoxygalactonojirimycin; 5-deoxy-L-arabinose; galactostatin bisulfate; 3′,4′,7-trihydroxyisoflavone; D-ribonolactone; N-octyl-4-epi-β-valienamine; phenylethyl β-D-thiogalactopyranoside; difluorotetrahydropyridothiazinone; 4-aminobenzyl 1-thio-β-D-galactopryranoside; a combination thereof; and a pharmaceutically acceptable salt thereof.

5. The PAS of claim 1 , wherein the PAS is maintained at a pH ranging between about 6.4 and about 7.6.

6. The PAS of claim 1 , wherein the phosphate source is present in an amount ranging from about 5 mM to about 50 mM, and wherein the phosphate source is selected from the group consisting of sodium monophosphate, sodium diphosphate, sodium triphosphate, and a combination thereof.

7. The PAS of claim 1 , wherein the citrate source is present in an amount ranging from about 2 mM to about 20 mM, and wherein the citrate source is selected from the group consisting of monosodium citrate, disodium citrate, trisodium citrate, citric acid, and a combination thereof.

8. The PAS of claim 1 , wherein the carbon source is present in an amount ranging from about 0.5 mM to about 50 mM, and wherein the carbon source is selected from the group consisting of acetate, glucose, and sucrose.

9. The PAS of claim 1 , wherein the acetate source is present in an amount ranging from about 10 mM to about 50 mM, and wherein the acetate source is selected from the group consisting of sodium acetate, potassium acetate, magnesium acetate, and a combination thereof.

10. The PAS of claim 1 , wherein the salt is selected from the group consisting of a sodium source, a chloride source, a potassium source, a magnesium source, a calcium source, and a combination thereof.

11. The PAS of claim 10 , wherein the sodium source is selected from the group consisting of sodium chloride, sodium citrate, sodium acetate, sodium phosphate, and a combination thereof.

12. The PAS of claim 10 , wherein the chloride source is selected from the group consisting of sodium chloride, magnesium chloride, potassium chloride, and a combination thereof.

13. The PAS of claim 10 , wherein the potassium source is selected from the group consisting of potassium chloride, potassium citrate, potassium acetate, potassium phosphate, potassium sulfate, and a combination thereof.

14. The PAS of claim 10 , wherein the magnesium source is selected from the group consisting of magnesium chloride, magnesium citrate, magnesium sulfate, and a combination thereof.

15. The PAS of claim 10 , wherein the calcium source is selected from the group consisting of calcium chloride, calcium acetate, calcium citrate, and a combination thereof.

16. A platelet additive solution (PAS) for storing platelets having a platelet surface, wherein active endogenous sialidase and β-galactosidase migrate to the platelet surface during storage, wherein sialic acid loss and galactose loss are reduced on the platelet surface of isolated platelets during storage, wherein the isolated platelets are obtained from one or more donors, the PAS comprises:

a. about 0.1 mM to about 100 mM of one or more β-galactosidase inhibitors and about 0.1 mM to about 100 mM of one or more sialidase inhibitors, and optionally an amount of one or more glycan-modifying agents, or a combination thereof; and

b. PAS components that includes a salt, a citrate source, a carbon source, an acetate source, or any combination thereof.