Platelet protection solution having beta-galactosidase and sialidase inhibitors
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.
1. A method of storing platelets, wherein isolated platelets are obtained from one or more donors, the method comprises:
a. contacting the isolated platelets with a Platelet Protection Solution (PPS) that comprises:
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, to thereby obtain a platelet composition.
2. The method 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 method of claim 1 , wherein the chloride source is present in the amount ranging between about 90 mM and about 110 mM.
4. The method of claim 1 , wherein the one or more sialidase inhibitor 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-hydroxyl-cyclopentane-1-carboxylic acid; a combination thereof; and a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the sialidase inhibitor is the sodium salt of 2,3-dehydro-2-deoxy-N-acetylneuraminic acid.
6. The method 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.
7. The method of claim 1 , wherein the isolated platelets are stored for a period of about 1to about 21days.
8. The method of claim 1 , wherein the isolated platelets are stored a temperature of between about 2° C. and about 25° C.
9. The method of claim 1 , further comprising cooling the platelet composition to a temperature below room temperature; storing the platelet composition for a period of time; and then rewarming the platelet composition back to room temperature.
10. The method of claim 1 , further comprising treating the population of platelets with the β-galactosidase inhibitor and the sialidase inhibitor, within a time period, wherein the time period is in a range between about 1minute and about 8hours.
11. The method of claim 1 , wherein the PPS is maintained at a pH ranging between about 6.4and about 7.6.
12. The method of claim 1 , wherein the phosphate source is selected from the group consisting of sodium monophosphate, sodium diphosphate, sodium triphosphate, and a combination thereof.
13. The method 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.
14. The method of claim 1 , wherein the acetate source is selected from the group consisting of sodium acetate, potassium acetate, magnesium acetate, and a combination thereof.
15. The method of claim 1 , wherein the sodium source is selected from the group consisting of sodium chloride, sodium acetate, sodium phosphate, and a combination thereof.
16. The method of claim 1 , wherein the chloride source is selected from the group consisting of sodium chloride, magnesium chloride, potassium chloride, and a combination thereof.
17. The method of claim 1 , wherein the potassium source is selected from the group consisting of potassium chloride, potassium acetate, potassium phosphate, potassium sulfate, and a combination thereof.
18. The method of claim 1 , wherein the magnesium source is selected from the group consisting of magnesium chloride, magnesium sulfate, and a combination thereof.
19. The method of claim 1 , wherein the calcium source is selected from the group consisting of calcium chloride, calcium acetate, and a combination thereof.
20. The method of claim 1 , wherein once the platelet composition is transfused into a recipient, circulation time of platelets is increased, as compared to circulation time of platelets that have not been subjected to Step a).
21. The method of claim 1 , wherein once the platelet composition is transfused into a recipient, platelet clearance of the platelets is reduced, as compared to platelet clearance of platelets that have not been subjected to Step a).
22. The method of claim 2 , wherein the sodium source comprises sodium citrate.
23. The method of claim 2 , wherein the potassium source comprises potassium citrate.
24. The method of claim 2 , wherein the magnesium source comprises magnesium citrate.
25. The method of claim 2 , wherein the calcium source comprises calcium citrate.