US 2014/0155498 A1 · Method of Manufacture of Stable Liquid Coagulation Factors

Abstract

A diagnostic or therapeutic formulation of stable liquid coagulation factors comprises at least one coagulation factor, at least one stabilizer, and optional additives. The stabilizer is either amylopectin, galatomannan polysaccharide, agarose, agaropectin, and gelatin, or a blend of amylopectin, galatomannan polysaccharide, agarose, agaropectin, and gelatin. A preferred additive is the zwitterionic buffer 3-[N-tris(hydroxymethyl)methylamino)-2-hydroxypropane sulfonic acid (TAPSO). The stable liquid coagulation factors can be used as reagents and controls in plasma clotting assays. In addition the therapeutic formulation can be used for factor replacement therapy. The stable liquid clotting factors are made by combining the coagulation factor(s), stabilizer(s), and additive(s) in a liquid carrier and sterilizing the mixture. Coagulation factors can be concentrated by selective precipitation from plasma. In addition, the clotting activity of the formulation can be adjusted by adding a factor concentrate to a less concentrated formulation.

Claims13

Dependent claims

A method for preparing a composition of matter, comprising:

(a) combining at least one stabilizer, a zwitterionic buffer and at least one coagulation factor in a liquid carrier to form a buffered solution, wherein the coagulation factor is a component in a cascade pathway that leads to clot formation and the stabilizer is selected from the group consisting of amylopectin, galatomannan polysaccharide, agarose, agaropectin, and gelatin, present in an amount sufficient to retard the degradation of the coagulation factor for at least one month when the composition of matter is stored at 2° C. to 8° C.;
(b) adjusting the pH of the solution to between about 6 to about 9;
and
(c) sterilizing the solution.

1 more element

A method for preparing a composition of matter containing at least one coagulation factor, comprising the steps of:

(a) mixing a liquid containing at least one coagulation factor with barium chloride in an amount sufficient to form a first precipitate and a first supernatant;
(b) isolating the first precipitate from the first supernatant;
(c) resuspending the first precipitate in a solution of ammonium sulfate to form a second precipitate and a second supernatant;
(d) separating the second supernatant from the second precipitate;
(e) increasing the concentration of ammonium sulfate in the second supernatant to form a third precipitate;
(f) collecting the third precipitate;
(g) forming a suspension of the third precipitate in dialysis buffer, the dialysis buffer comprising:
(i) a liquid carrier;
(ii) at least one stabilizer, wherein the stabilizer is selected from the group consisting of amylopectin, galatomannan polysaccharide, agarose, agaropectin, and gelatin;
and
(iii) at least one additive selected from the group consisting of a zwitterionic buffer, an antibiotic agent, and sodium citrate;
and
(h) dialyzing the suspension against dialysis buffer, wherein the suspension is held within a dialysis membrane capable of retaining the coagulation factor.

10 more elements

An assay for detecting clot formation comprising:

(a) combining a sample and a reagent, wherein the reagent is a composition of matter comprising a phospholipid coagulation factor in the liquid carrier that mediates a cascade pathway that leads to clot formation selected from the group consisting essentially of thromboplastin cephaloplastin, cephalin, and soy phosphatides;
and at least one stabilizer for the phospholipid coagulation factor in the liquid carrier selected from the group consisting of amylopectin, galatomannan polysaccharide, agarose, agaropectin, and gelatin, the stabilizer being present in an amount sufficient to retard the degradation of the coagulation factor for at least one month when the composition of matter is stored at 2° C. to 8° C.;
(b) initiating clot formation when calcium ions are introduced with the sample and reagent;
and
(c) determining a sample clotting time.

2 more elements

Dependencies are inferred from the claim text.

Method of Manufacture of Stable Liquid Coagulation Factors

Life of this patent

Method of Manufacture of Stable Liquid Coagulation Factors

Life of this patent

Abstract

Claims13