Ethanol dependence of alpha1 antitrypsin C-terminal lys truncation by basic carboxypeptidases
View Patent ↗Methods of preparing alpha-1-antiproteinase inhibitor and controlling the amount of des-lys alpha-1-antiproteinase inhibitor in the preparation, and compositions comprising the same, as well as methods of treatment using the same are provided.
1. A method of making an alpha-1-proteinase inhibitor composition comprising des-lys aloha-1 proteinase inhibitor from human plasma, the method comprising the step of:
treating a plasma precipitate comprising alpha-1-proteinase inhibitor with ethanol at a concentration of from 30% to 50%,
wherein the plasma precipitate is selected from the group consisting of a Cohn fraction IV-1 precipitate and a Cohn fraction IV-1+IV-4 precipitate, and
wherein the amount of des-lys alpha-1-proteinase inhibitor is increased.
2. The method of claim 1 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is more than 70% of total alpha-1-proteinase inhibitor in the composition.
3. The method of claim 1 , wherein the amount of des-lys alpha-1-proteinase inhibitor in the composition treated with ethanol is more than 75% of total alpha-1-proteinase inhibitor in the composition.
4. The method of claim 1 , comprising treating the Cohn fraction IV-1 or IV-1+IV-4 precipitate with ethanol at a final concentration of 50%.
5. The method of claim 1 , comprising treating the Cohn fraction IV-1 or IV-1+IV-4 precipitate with ethanol at a final concentration of 40%.
6. The method of claim 1 , comprising treating the Cohn fraction IV-1 or IV-1+IV-4 precipitate with ethanol at a final concentration of less than 45% but greater than 35%.
7. The method of claim 1 , comprising treating the Cohn fraction IV-1 or IV-1+IV-4 precipitate at a pH greater than pH 5.9.
8. The method of claim 1 , wherein the plasma precipitate is a Cohn fraction IV-1 precipitate.
9. The method of claim 1 , wherein the plasma precipitate is a Cohn fraction IV-1÷IV-4 precipitate.
10. An alpha-1-proteinase inhibitor composition comprising a physiologically acceptable carrier and an amount of des-lys alpha-1-proteinase inhibitor that is more than about 70% of total alpha-1-proteinase inhibitor in the composition, the composition made using the method of claim 1 .
11. An alpha-1-proteinase inhibitor composition comprising a physiologically acceptable carrier and an amount of des-lys alpha-1-proteinase inhibitor that is more than about 75% of total alpha-1-proteinase inhibitor in the composition, the composition made using the method of claim 1 .