Not Applicable
Fibrin glues, also called fibrin adhesives or sealants, are known for uses in a medical context. Generally, a fibrin glue is obtained by admixing fibrinogen and thrombin containing components. The components are mixed, allowing the thrombin to convert the fibrinogen to fibrin monomers. A number of methods for the production of fibrin glues are known, as illustrated by: Thompson et al., xe2x80x9cFibrin Glue: A Review of Its Preparation, Efficacy, and Adverse Effects as a Topical Hemostat,xe2x80x9d Drug Intelligence and Clinical Pharmacy 22: 946-52 (1988); Brennan, xe2x80x9cFibrin Glue,xe2x80x9d Blood Reviews 5: 240-44 (1991); Stechison, xe2x80x9cRapid Polymerizing Fibrin Glue from Autologous or Single Donor Blood: Preparation and Indications,xe2x80x9d J. Neurosurgery 76: 626-28 (1992); and Toma et al. xe2x80x9cAutologous Fibrin Glue in the Repair of Dural Defects in Craniofacial Resections,xe2x80x9d J. Laryngology and Otology 106: 356-57 (1992). (The respective contents of publications cited in this description hereby are incorporated by reference.)
The fibrinogen component of the composition can be obtained by conventional methodology. Examples of such methods include centrifugation, cryoprecipitation and precipitation using polyethylene glycol, ether, ethanol, glycine or ammonium sulfate. Methods of obtaining suitable fibrinogen are disclosed, for example, by Brennan, xe2x80x9cFibrin Glue,xe2x80x9d Blood Reviews 5: 240-244 (1991). Further examples of fibrin components are disclosed in U.S. Pat. Nos. 5,290,918 and 5,395,923.
The thrombin component of the composition is also well known in the art and can be obtained by conventional methods, including recombinant methods. Bovine and human derived thrombins are illustrative of available thrombins well known in the art.
Application of the fibrin glue can be accomplished in a number of ways known in the art. In one method, the admixture is drawn into a syringe and ejected via an appropriate sized needle. In another method a double barrel syringe is used. Other conventional techniques employ a microdrop delivery system, a spray application via a multi-channel catheter which is fixed to a pressurized gas source, or a carrier, such as collagen fleece, dura, or a graft. Additionally, a number of special applicators are commercially available.
Numerous uses for fibrin glues are known. Fibrin glues are used in a variety of medical procedures as hemostatic agents, sealants and adhesives. For example, see Chisholm et al., xe2x80x9cFibrin Sealant as a Plug for the Post Liver Biopsy Needle Track,xe2x80x9d Clinical Radiology 40: 627-28 (1989); Toma et al., xe2x80x9cAutologous Fibrin Glue in the Repair of Dural Defects in Craniofacial Resections,xe2x80x9d J. Laryngology and Otology 106: 356-57 (1992); Kjaergard et al., xe2x80x9cAutologous Fibrin Glue Preparation and Clinical Use in Thoracic Surgery,xe2x80x9d Eur. J. Cardio-Thorc. Surg. 6: 52-54 (1992); Thompson et al., xe2x80x9cFibrin Glue: A Review of Its Preparation, Efficacy, and Adverse Effects as a Topical Hemostat,xe2x80x9d Drug Intelligence and Clinical Pharmacy 22: 946-52 (1988); Brennan, xe2x80x9cFibrin Glue,xe2x80x9d Blood Reviews 5: 240-44 (1991).
Available fibrin glues, however, have a number of significant disadvantages. The fibrinogen and thrombin components must be mixed just prior to use. Admixing too early can result in clotting before it can be applied. Thus, medical professionals are forced to divert their attention for a significant amount of time to prepare the fibrin glue. Early clotting also causes problems in application, such as clogging in the needle or applicator. Additionally, preparation of the fibrin glue can involve complex and time-consuming efforts to establish a workable mix of the fibrinogen and thrombin components. Still further, available fibrin glues may insufficiently adhere to the wound, or may provide inadequate strength to the wound during the healing process.
The present invention relates to a fibrin glue composition comprising a biocompatible and bioabsorbable material, i.e., a biomaterial, of a hyaluronic acid (HA) or a hyaluronic acid derivative. The material may be either nonfilamentous (a film) or a woven or nonwoven fabric. The fibrin glues of the present invention have fibrinogen and thrombin applied to or chemically bonded to the HA or HA derivative material. Additional elements also can be applied to the material. Exemplary of these additional elements are further coagulation factors, anti-fibrinolytics, stabilizers and biologically active substances.
The fibrinogen, thrombin and, optionally, other elements can be applied to the hyaluronic acid derivative film as a dry preparation, as an aqueous or nonaqueous preparation, or as a combination thereof.