Bristol-myers Squibb Compnay

E. R. Squibb Sons, Inc.

Peter A Edwardson

Stewart A Cederholm-Williams

Derek A Hollingsbee

John E Fairbrother

Ronald S Gardner

Steven James Burton

James Christopher Pearson

Niels Erik Holm

The subject invention relates to fibrin sealants. More specifically, the subject invention relates to the use of a fibrin sealant wherein a composition comprising fibrin monomer or a composition comprising noncrosslinked fibrin is utilized as a component of the fibrin sealant.

Method of making a composition comprising a fibrin monomer

Fibrin sealant compositions and methods for utilizing same

Compositions and methods for avidin immobilized on an inert support material, e.g. agarose, are disclosed. The compositions have high activity levels of avidin and may further include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the avidin agarose during lyophilization and terminal sterilization processes. These compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomer useful for fibrin sealants. The fibrin is prepared by subjecting a fibrinogen-containing composition to a biotinylated enzyme to convert the fibrinogen in the composition to a corresponding fibrin monomer. A fibrin monomer/biotinylated enzyme mixture is formed. A material comprising an avidin/inert support composition having 1000 biotin binding units of activity per gram of the composition, a bulking agent and a protectant, is then introduced into the enzyme mixture to form a complex of the material and the biotinylated enzyme. The complex and enzyme are then removed therefrom to recover a fibrin monomer. Bulking agents selected from nonionic water soluble compounds are used.

Method of producing a fibrin monomer using a biotinylated enzyme and

Compositions and methods for avidin or protein having affinity for biotin immobilized on an inert support material, e.g., agarose, are disclosed. The compositions have high activity levels for binding biotin and may include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the composition during lyophilization and terminal sterilization processes. The compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomers useful for fibrin sealants.

Stable composition of immobilized protein having affinity for biotin

This invention is directed to solid compositions, for example, lyophilized forms, of fibrin monomer. These compositions are useful wherever fibrin monomer could be employed, e.g., as a surgical sealant to provide hemostasis.

Solid compositions of fibrin monomer

Compositions and methods for avidin immobilized on an inert support material, e.g., agarose, are disclosed. The compositions have high activity levels of avidin and may further include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the avidin agarose during lyophilization and terminal sterilization processes. A dry composition, and wet compositions such as a gel, slurry or suspension having avidin immobilized on an inert support material are disclosed. The dry composition has at least 1000 biotin binding units of activity, and the wet compositions have at least 50 units of binding activity. These compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomer useful for fibrin sealants.

Gel, slurry or suspension containing immobilized avidin having high

A method and a device for separating a component, such as fibrin monomer from blood, by centrifugation, involve feeding of blood admixed an anticoagulant to a first annular chamber in a device, where the annular chamber is defined by a cylindrical outer wall and a cylindrical inner wall, both walls extending coaxially about a common axis, as well as by a top wall and a bottom wall. The top wall or the bottom wall is formed by a piston body displaceable within the first chamber. This method involves furthermore a centrifugation of the device about the said common axis to substantially separate blood into a cell fraction and a plasma fraction followed by the resulting plasma fraction being transferred while influenced by the piston body to a second chamber defined by an outer cylindrical wall. The outer cylindrical wall extends coaxially with the said common axis, whereby a fraction with fibrin I is caused to be separated in the second chamber while a suitable enzyme is being added. The separation of fibrin monomer from the plasma fraction in the second chamber is carried out during continued centrifugation whereby a fibrin polymer is deposited on the cylindrical outer wall of said second chamber, whereafter the fluid fraction collected at the bottom of the second chamber is transferred while influenced by the piston body to the first chamber. The fraction with fibrin polymer remaining in the second chamber is substantially deposited on the cylindrical wall and is caused to be dissolved by addition of a solvent and by centrifugation, whereafter it is transferred to a receiving container by passing after addition of a binder to the enzyme through a filter removing said enzyme, whereby a fibrin monomer containing solution is provided.

Method and device for separating a component such as fibrin I from blood

The invention relates to fibrin sealants. More specifically, the invention relates to the preparation of a fibrin polymer wherein the polymer is substantially free of the enzyme.

The subject invention relates to fibrin sealants. More specifically, the subject invention relates to the use of a fibrin sealant wherein a composition comprising fibrin polymer is utilized as a component of the fibrin sealant.

Novel kits for the preparation of a fibrin sealant are disclosed. In one kit a first component is fibrin monomer which can be polymerized to form a fibrin sealant when combined with the second component which is distilled water or an alkaline buffer.

Kit for preparing a fibrin sealant

The present invention relates to a solid support, e.g., a suture, bandage, dressing or prosthesis, and a nondynamic fibrin monomer. The nondynamic fibrin monomer is readily capable of being converted to a fibrin polymer which has sealant and hemostasis properties.

Nondynamic fibrin monomer on bandages, sutures, prostheses and dressings

The subject invention relates to methods and compositions using nondynamic fibrin monomer which is selectively converted to a fibrin polymer which serves as the fibrin sealant.

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Chester, United Kingdom

Peter A Edwardson