Platelet Protection Solution Having Beta-Galactosidase and Sialidase Inhibitors

Abstract

The present invention relates to a platelet protection solution (PPS) having an amount of one or more β-galactosidase inhibitors with or without an amount of one or more sialidase inhibitors, and optionally one or more glycan-modifying agents; and one or more of PPS components that include a salt, a citrate source, a carbon source, or any combination thereof.

What is claimed is: 
     
         1 . A platelet protection solution (PPS), comprising:
 a. an amount of one or more β-galactosidase inhibitors and an amount of one or more sialidase inhibitors, and optionally an amount of one or more glycan-modifying agents;   b. PPS components in a form of salt, consisting essentially of:   a sodium source in an amount ranging between about 100 mM and about 300 mM;   a chloride source in an amount ranging between about 40 mM and about 110 mM;   an acetate source in an amount ranging between about 10 mM and about 50 mM;   a phosphate source in an amount ranging between about 5 mM and about 50 mM;   a potassium source in an amount ranging between about 0.5 mM and about 10 mM; and   a magnesium source in an amount ranging between about 0.5 mM and about 5.0 mM.   
     
     
         2 . The PPS of  claim 1 , further comprising at least one of the group consisting of:
 a. a calcium source in an amount ranging between about 0.1 mM and about 2.5 mM;   b. a glucose source in an amount ranging between about 0.1 mM and about 30 mM;   c. a citrate source in an amount ranging between about 2 mM and about 20 mM; and   d. a combination thereof.   
     
     
         3 . The PPS of  claim 1 , wherein the chloride source is present in the amount ranging between about 90 mM and about 110 mM; 
     
     
         4 . The PPS of  claim 1 , wherein the PPS is maintained at a pH ranging between about 6.4 and about 7.6. 
     
     
         5 . The PPS of  claim 1 , wherein the phosphate source is selected from the group consisting of sodium monophosphate, sodium diphosphate, sodium triphosphate, and a combination thereof. 
     
     
         6 . The PPS of  claim 2 , wherein the citrate source is selected from the group consisting of monosodium citrate, disodium citrate, trisodium citrate, citric acid, and a combination thereof. 
     
     
         7 . The PPS of  claim 1 , wherein the acetate source is selected from the group consisting of sodium acetate, potassium acetate, magnesium acetate, and a combination thereof. 
     
     
         8 . The PPS of  claim 2 , wherein the sodium source is selected from the group consisting of sodium chloride, sodium citrate, sodium acetate, sodium phosphate, and a combination thereof. 
     
     
         9 . The PPS of  claim 1 , wherein the chloride source is selected from the group consisting of sodium chloride, magnesium chloride, potassium chloride, and a combination thereof. 
     
     
         10 . The PPS of  claim 1 , 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. 
     
     
         11 . The PPS of  claim 1 , wherein the magnesium source is selected from the group consisting of magnesium chloride, magnesium citrate, magnesium sulfate, and a combination thereof. 
     
     
         12 . The PPS of  claim 2 , wherein the calcium source is selected from the group consisting calcium chloride, calcium acetate, calcium citrate, and a combination thereof. 
     
     
         13 . The PPS of  claim 1 , wherein the sialidase inhibitor is selected from the group consisting of: fetuin; 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA); ethyl (3R,4R,5 S)-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-carboxylicacid; (4S,5R,6R)-5-acetamido-4-carbamimidamido-6-[(1R,2R)-3-hydroxy-2-methoxypropyl]-5,6-dihydro-4H-pyran-2-carboxylicacid; (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. 
     
     
         14 . The PPS of  claim 1 , wherein the one or more β-galactosidase inhibitors are 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. 
     
     
         15 . A platelet composition comprising:
 a. isolated platelets;   b. plasma; and   c. a PPS that comprises:
 i. one or more β-galactosidase inhibitors and one or more sialidase inhibitors, and optionally one or more glycan-modifying agents; and 
 ii. PPS components in a form of salt; consisting essentially of: 
   a sodium source in an amount ranging between about 100 mM and about 300 mM;   a chloride source in an amount ranging between about 40 mM and about 110 mM;   an acetate source in an amount ranging between about 10 mM and about 50 mM;   a phosphate source in an amount ranging between about 5 mM and about 50 mM;   a potassium source in an amount ranging between about 0.5 mM and about 10 mM; and   a magnesium source in an amount ranging between about 0.5 mM and about 5.0 mM;   wherein the platelet composition is maintained at a pH ranging between about 6.4 and about 7.6.   
     
     
         16 . The platelet composition of  claim 15 , further comprising at least one of the group consisting of:
 a. a calcium source in an amount ranging between about 0.1 mM and about 2.5 mM;   b. a glucose source in an amount ranging between about 0.1 mM and about 30 mM;   c. a citrate source in an amount ranging between about 2 mM and about 20 mM; and   d. a combination thereof.   
     
     
         17 . The platelet composition of  claim 15 , wherein the chloride source is present in the amount ranging between about 90 mM and about 110 mM. 
     
     
         18 . The platelet composition of  claim 15 , wherein the plasma is present in an amount ranging between about 1% and about 50% by volume. 
     
     
         19 . The platelet composition of  claim 15 , wherein the platelet protection solution is present in an amount ranging between about 50% and about 99% by volume. 
     
     
         20 . A bag or container that comprises:
 a. a bag or container suitable for platelet storage; and   b. a PPS comprising:
 i. an amount of one or more β-galactosidase inhibitors and an amount of one or more sialidase inhibitors, and optionally an amount of one or more glycan-modifying agents, or a combination thereof; and 
 ii. PPS components in a form of salt, consisting essentially of: 
   a sodium source in an amount ranging between about 100 mM and about 300 mM;   a chloride source in an amount ranging between about 40 mM and about 110 mM;   an acetate source in an amount ranging between about 10 mM and about 50 mM;   a phosphate source in an amount ranging between about 5 mM and about 50 mM;   a potassium source in an amount ranging between about 0.5 mM and about 10 mM; and   a magnesium source in an amount ranging between about 0.5 mM and about 5.0 mM.   
     
     
         21 . The bag or container of  claim 20 , further comprising at least one of the group consisting of:
 a. a calcium source in an amount ranging between about 0.1 mM and about 2.5 mM;   b. a glucose source in an amount ranging between about 0.1 mM and about 30 mM;   c. a citrate source in an amount ranging between about 2 mM and about 20 mM; and   d. a combination thereof.   
     
     
         22 . The bag or container of  claim 20 , wherein the chloride source is present in the amount ranging between about 90 mM and about 110 mM. 
     
     
         23 . The bag or container of  claim 20 , further comprising isolated platelets. 
     
     
         24 . The bag or container of  claim 20 , wherein the PPS is maintained at a pH ranging between about 6.4 and about 7.6.