Fibrinogen and thrombin solutions for a fibrin sealant and fibrin sealant kit

Inventors

Gulle, Heinz • Singh, Rahul Kumar • Rabas, Julia • Reinauer, Eva • Grosso, Stella

Assignees

Baxter Healthcare SA • Leukocare AG • Baxter International Inc

Abstract

Disclosed are a fibrinogen solution and a thrombin solution. The fibrinogen solution comprises fibrinogen at a concentration of at least 40 mg/ml, factor XIII, pharmaceutically acceptable additives and water. The dynamic viscosity of the fibrinogen solution measured at 20° C. increases at most by 35% after storing the solution at 20° C. for 30 days. The thrombin solution comprises thrombin, pharmaceutically acceptable additives and water. The thrombin activity decreases at most by 15% after storing the solution at 25° C. for 14 days. Also disclosed is a fibrin sealant kit with a first container comprising the fibrinogen solution and a second container comprising the thrombin solution. Further, methods for preparing a fibrin sealant and methods for treating a wound are disclosed.

Core Innovation

The invention provides a fibrinogen solution engineered for minimal viscosity increase after storage. The fibrinogen solution consists essentially of human fibrinogen, human Factor XIII, synthetic aprotinin, arginine, histidine, guanidine-HCl, and NaCl, with a defined total protein concentration and osmolality. The fibrinogen solution is characterized by viscosity behavior intended to remain within specification after storage at room temperature conditions.

The invention also provides a room temperature storage stable thrombin solution engineered for minimal activity loss after storage. The thrombin solution consists essentially of thrombin, CaCl2, glycine, histidine, methionine, guanidine-HCl, and cyclodextrin, with a defined pH. The thrombin solution is designed to retain thrombin activity within specification after storage.

The invention further relates to a fibrin sealant kit architecture in which the fibrinogen solution and the thrombin solution are supplied in separate containers suitable for combining to form a fibrin sealant. The disclosed kit includes first and second containers, including pre-filled syringes as specified, and supports thawing and storing of the frozen components at defined temperatures for at least about three days before combining.

The disclosed fibrin sealant kit and the specific fibrinogen and thrombin solutions address usability constraints associated with existing thrombin/fibrinogen systems by optimizing additive composition to control fibrinogen viscosity and thrombin activity retention during storage, as supported by experimental examples in the provided content.

Claims Coverage

The provided independent claims cover two main compositions: a specifically defined fibrinogen solution and a specifically defined room-temperature storage-stable thrombin solution, with additional claim dependents refining viscosity behavior, viscosity change after storage, thrombin activity retention, and kit/workflow parameters. In total, the main claim set introduces six inventive-feature themes across the independent claim families: controlled fibrinogen composition with specified total protein and osmolality, constrained fibrinogen viscosity at 20°C, constrained fibrinogen viscosity increase after room-temperature storage, a constrained thrombin solution composition with defined pH, constrained thrombin activity retention after storage, and kit/combining/containers workflow elements for forming a fibrin sealant.

Across the independent claim families, the claim coverage centers on a defined fibrinogen solution composition with specified total protein concentration and osmolality and a defined room-temperature storage-stable thrombin solution composition with defined pH, together with dependents that constrain viscosity behavior and thrombin activity retention after storage. Additional dependents define how fibrin sealant is formed by combining the specified solutions, including kit-based container and workflow features such as thawing and storing at defined temperatures for at least three days and using pre-filled syringes for the component containers.

Stated Advantages

Documented Applications