Process for Producing a Plasma Protein-Containing Medicament
There is disclosed a method of preparing a plasma protein-containing medicament from citrated plasma or from a citrate-containing plasma fraction, the medicament being substantially free from undesired metals, which method comprises the following steps exchanging the citrate and optionally citrate-bound metals in a plasma-protein-containing solution for a water-soluble mono- or dicarboxylate or for an organic mono- or dicarboxylic acid under non-precipitating conditions, recovering the plasma protein or the plasma proteins, and finishing the medicament.
1 - 13 . (canceled)
14 . A plasma-protein-containing medicament obtained from citrated plasma or from a citrate-containing plasma fraction, wherein the medicament has a reduced concentration of undesired metals selected from the group consisting of aluminum, cadmium, zinc, lead and iron, wherein the medicament is obtained by a method comprising the steps of:
(a) obtaining citrated plasma or citrate-containing plasma fraction by Cohn fractionation;
(b) adding to the citrated plasma or citrate-containing plasma fraction a compound to achieve a solution having a compound concentration of between 0.001 and 1.00 mol/liter, wherein the compound is selected from the group consisting of a monocarboxylate, a dicarboxylate, a monocarboxylic acid and a dicarboxylic acid;
(c) exchanging citrate and citrate-bound metals that may be present in the plasma or plasma fraction with the compound by diafiltration, ultrafiltration or chromatography at a temperature above 0° C. to 50° C. and at a pH of 6 to 8, under non-precipitating conditions, thereby reducing the concentration of citrate and the undesired metals that may have been present;
(d) recovering one or more plasma proteins; and
(e) finishing the medicament.
15 . The plasma-protein-containing medicament as set forth in claim 14 , wherein the compound has 2 to 20 carbon atoms.
16 . The plasma-protein-containing medicament as set forth in claim 14 , wherein the compound is selected from the group consisting of caprylate, tartrate, hexanoic acid and acetate.
17 . The plasma-protein-containing medicament as set forth in claim 14 , wherein the plasma proteins for the medicament are selected from the group consisting of albumin, coagulation factors, fibrinolysis factors, immunoglobulins and glycoproteins.
18 . The plasma-protein-containing medicament as set forth in claim 14 , wherein the medicament has a content of undesired metals of less than 100 μg/l.
19 . The plasma-protein-containing medicament as set forth in claim 14 , wherein the medicament has a content of undesired metals of less than 10 μg/l.
20 . The plasma-protein-containing medicament as set forth in claim 14 , wherein the content of undesired metals is less than 200 ng/l.
21 . A plasma-protein-containing medicament obtained from a Cohn fraction comprising plasma proteins and citrate, wherein the medicament has a reduced concentration of undesired metals selected from the group consisting of aluminum, cadmium, zinc, lead and iron, wherein the medicament is obtained by a method comprising the steps of:
(a) adding to the Cohn fraction, a compound to achieve a solution having the compound concentration of between 0.001 and 1.00 mol/liter, wherein the compound is selected from the group consisting of a monocarboxylate, a dicarboxylate, a monocarboxylic acid and a dicarboxylic acid;
(b) exchanging the citrate and citrate-bound metals that may be present in the Cohn fraction with the compound by diafiltration, ultrafiltration or chromatography at a temperature above 0° C. to 50° C. and at a pH of 6 to 8, under non-precipitating conditions, thereby reducing the concentration of citrate and undesired metals that may have been present;
(c) recovering one or more plasma proteins; and
(d) finishing the medicament.
22 . The plasma-protein-containing medicament as set forth in claim 21 , wherein the compound has 2 to 20 carbon atoms.
23 . The plasma-protein-containing medicament as set forth in claim 21 , wherein the compound is selected from the group consisting of caprylate, tartrate, hexanoic acid and acetate.
24 . The plasma-protein-containing medicament as set forth in claim 21 , wherein the plasma proteins for the medicament are selected from the group consisting of albumin, coagulation factors, fibrinolysis factors, immunoglobulins and glycoproteins.
25 . The plasma-protein-containing medicament as set forth in claim 21 , wherein the medicament has a content of undesired metals of less than 100 μg/l.
26 . The plasma-protein-containing medicament as set forth in claim 21 , wherein the medicament has a content of undesired metals of less than 10 μg/l.
27 . The plasma-protein-containing medicament as set forth in claim wherein the medicament has a content of undesired metals of less than 200 ng/l.