Therapeutic human albumin solutions with low prekallikrein activator (PKA) activity and process for obtaining them
View Patent ↗The invention discloses a purified albumin solution of human origin with low prekallicrein activator (PKA) activity and stability over time characterized in that it has an antithrombin content equal to or greater than 0.03 mg/g of albumin, and a process for production thereof by the partial extraction of the antithrombin during fractionation of the human plasma.
1. A process for reducing prekallikrein activator (PKA) activity in purified albumin solutions comprising:
(a) fractionating human plasma;
(b) extracting, by chromatography, a portion of antithrombin from the human plasma; and
(c) separating a purified albumin solution from the fractionation of human plasma,
wherein the purified albumin solution has an active antithrombin content of 0.03 to 0.1 mg per g albumin, and a PKA activity of less than 35 IU/ml when measured as a 20% (w/v) albumin solution on storage at 5° C. at 12 months.
2. The process according to claim 1 , further comprising a step of extracting, by chromatography, a portion of antithrombin from a cryoprecipitate supernatant obtained from fractionating the human plasma.
3. The process according to claim 1 , further comprising a step of extracting, by chromatography, a portion of antithrombin from a fraction I supernatant obtained from fractionating the human plasma.
4. The process according to claim 1 , further comprising a step of extracting, by chromatography, a portion of antithrombin from a fraction II+III supernatant obtained from fractionating the human plasma.
5. The process according to claim 1 , further comprising a step of removing a portion of the antithrombin by affinity chromatography.
6. The process according to claim 1 , further comprising a step of removing a portion of the antithrombin by ion-exchange chromatography.
7. The process of claim 1 , further comprising the step of combining two or more purified albumin solutions of differing antithrombin concentration to produce an albumin solution having at least 0.03 mg antithrombin per g of albumin.
8. The process of claim 7 , wherein at least one of the combined albumin solutions has not been subjected to an antithrombin reduction step.
9. The process of claim 1 , wherein the purified albumin solution has a PKA activity of 5.7 IU/ml or less when measured as a 20% (w/v) albumin solution on storage at 5° C. at 12 months.
10. The process of claim 1 , wherein the resulting albumin solution has PKA activity ≦3 IU/ml when measured as a 20% (w/v) albumin solution on storage at 5° C. at 1 month.
11. The process of claim 1 , further comprising a step of pooling purified albumin solutions of differing active antithrombin content.