Although fibrin glue is more commonly used to repair wounds in surgical procedures and other clinical treatments, the effective application of the fibrin glue is still hindered by several difficulties. Specifically, the production of a high concentration fibrin glue generally requires long hours of processing. Such time consuming processes limit the practical application and utility of such production cycles in an urgent application. Some production processes are also limited by the fact that chemical agents will cause fibrin glue protein to denature. Furthermore, in some production processes, the plasma is exposed to air and environments where viruses or bacteria may enter into the plasma mixtures and cause contamination. Incompatible blood may also cause immunological reactions. These risks further limit the practical usefulness and the safety of such applications when the fibrin glue is employed as a wound sealant.
Fibrin glue produced from basic physiological functions is becoming more popular for application to a variety of surgical procedures. A stable fibrin clot is produced when the fibrinogen, thrombin and factor XIII are activated in the presence of calcium ions. The application of the fibrin glue to the wound sites allows the restoration of the structural properties of the wounds by the glue. Furthermore, the fibrin glue contains components that can stimulate the repairing, or healing of the wounds.
In U.S. Pat. No. 4,627,879, entitled "Fibrin Adhesive Prepared As A Concentrate From Single Donor Fresh Frozen Plasma", Rose et al. discloses a method of preparing a cryo-precipitated suspension containing fibrinogen and factor XIII useful as a precursor in the preparation of a fibrin glue. The method includes the steps of (a) freezing fresh frozen plasma from a single donor, such as a human or other animal, at -80.degree. C. for at least six to twelve hours; (b) raising the temperature of the frozen plasma to about room temperature so as to form a supernatant and cryo-precipitated suspension containing fibrinogen and factor XIII; and (c) recovering the cryo-precipitated suspension. The cryo-precipitated suspension may be useful as a precursor for preparing the fibrin glue. However, the Rose et al. invention does not provide an effective method to produce a fibrin glue in a sufficient concentration and with strong adhesion properties for clinical and surgical applications. In addition, the long, time-consuming process of [preparing the] fibrin glue preparation also limits its practical usefulness.
In U.S. Pat. No. 5,185,001, entitled "Method of Preparing Autologous Plasma Fibrin and Application Apparatus Therefor" issued on Feb. 9, 1993), Galanakis discloses a method of preparing autologous plasma fibrin perioperatively to induce local hemostasis wherein the autologous plasma fibrin is simultaneously expelled onto a treatment site along with a physiologically acceptable thrombin solution to effect hemostasis at the site. Galanakis also discloses an apparatus for simultaneously expelling the contents of vessels which separately contain the autologous plasma fibrin and thrombin solution. Further disclosed in the Galanakis patent are a kit for obtaining a sample of blood, extracting plasma fibrin therefrom, as well as all necessary syringes, needles and reagents. The apparatus and method for preparing the autologous plasma fibrin disclosed in the Galanakis patent is a low concentration plasma fibrin which is suitable for inducing local hemostasis which may be useful for smaller wounds. However, the plasma fibrin added with the thrombin solution would not provide a total solution for surgical applications where larger wounds are usually involved.
In U.S. Pat. No. 5,226,877, entitled "Method and Apparatus for Preparing Fibrinogen Adhesive From Whole Blood" (issued on Jul. 13, 1993), Epstein discloses a process and an apparatus for one-step preparation of a fibrinogen adhesive by polyethylene glycol-mediated precipitation from plasma. The methods and apparatus permit preparation of an autologous fibrinogen adhesive composition from the patient during surgery and can be applied generally to provide such compositions. Also disclosed in the Epstein invention are an apparatus and method for application of a sealant comprised of the fibrinogen adhesive composition. According to Epstein, after the plasma is separated from the red blood cells, it is treated directly at the ambient temperature without prior treatment to remove thrombin, with a physiologically acceptable nontoxic precipitant. A preferred precipitant is a nontoxic polymer, e.g. polyvinyl alcohol and polyethylene glycol (PEG). The precipitant is supplied as concentrated solution to mix with plasma to yield a concentration effective in precipitating the adhesive composition.
The Epstein method is useful in producing the fibrinogen adhesives; however it has a problem wherein the precipitant, including the nontoxic polymers, may cause unknown side effects when added to the blood plasma, as these precipitants are not removed from the adhesive and are applied directly to the blood of a patient. Additives which are not removed are causes for concern in that unknown, harmful agents may be introduced, and may not be easily discoverable until many years later. The Epstein method also produces albumin precipitants and other complex proteins that will influence the fibrin glue's adhesive and hemostatic effects.
In U.S. Pat. No. 5,290,552, entitled "Surgical Adhesive Material" (issued Mar. 1, 1994), Sierra et al. disclose a surgical adhesive which is comprised, in an aqueous composition, of fibrinogen, FXIII, collagen, thrombin, Ca.sup.++ and an optionally antifibrinolytic agent. In order to extract the fibrinogen, which constitutes the adhesive component from the patient's own plasma, the plasma cryo-precipitate is prepared by freezing the plasma to -20.degree. C. and then slowly thawed overnight. The thawed plasma is then centrifuged to harvest the plasma precipitate. This process is disadvantageous in that extra long hours are required to produce the surgical adhesive through the low temperature process. Although the fibrinogen components are produced in a closed system, higher risks may be involved during the preparation process due to the possible contamination of the fibrinogen adhesive through contact with air and the possibility of undesirable immunological response due to the addition of collagen.
In U.S. Pat. No. 5,510,102, entitled "Plasma and Polymer Containing Surgical Hemostatic Adhesive" (issued on Apr. 23, 1996), Cochrum discloses an autologous platelet-rich plasma and a bio-compatible polymer containing hemostatic adhesive agents. The agents have strong hemostatic properties when applied to a bleeding wound or vessel. Although the platelet-rich plasma may be produced from the method disclosed in the Cochrum patented invention, risks of unknown side effects to the human body may still be a concern due to the addition of the bio-compatible polymer into the plasma. This is especially true when the mixture is to be applied directly to the vessel wounds wherein such plasma will be absorbed and carried throughout the body via blood vessels. Such risks may preclude the Cochrum plasma from being used in surgical or clinical applications.
In U.S. Pat. No. 5,520,885, entitled "Fibrinogen Processing Apparatus Method and Container", Coelho et al. disclose an instrumentality for promulgating the cryo-precipitation of fibrinogen from a blood product. The method, apparatus and container are disclosed in this patented invention; however, as discussed above, when a cryo-precipitation method is employed, long hours of freezing and thawing are required, which renders the application of such methods and apparatus to practical surgical or clinical environments ineffective.
Therefore, a need still exists in the art of fibrin glue production to provide a novel and effective process such that the production of the fibrin glue adhesive can be accomplished in less time. Furthermore, the fibrinogen adhesive produced must be free of contamination and additives such that application of the fibrin glue to the human body in surgical and clinical treatments can be safely administered.