Surgery – Instruments – Sutureless closure
Reexamination Certificate
1999-09-20
2001-02-06
Jackson, Gary (Department: 3731)
Surgery
Instruments
Sutureless closure
C530S356000, C530S402000, C530S408000
Reexamination Certificate
active
06183498
ABSTRACT:
BACKGROUND OF THE INVENTION
The ability to establish bonding between biological tissues has long been a goal of biomedical researchers. Attempts to provide desired adhesion through mechanical bonding have proven to be neither convenient nor permanent. For this reason, much attention was devoted to developing synthetic polymers as biomedical adhesives. Such materials, however, have been observed to induce inflammatory tissue reactions. Moreover, the ability of these materials to establish permanent bonding under physiological conditions has not been fully realized.
The known toxicity associated with synthetic adhesives has led investigations towards a development of biologically derived adhesives as bonding materials. Among such adhesives, fibrin based glues have commanded considerable attention. Commercial fibrin tissue adhesives are derived from human plasma and, therefore, pose potential health risks such as adverse immunogenic reactions and transmission of infectious agents. Moreover, the bond strength imparted by such adhesives is relatively weak compared to collagen adhesives.
Collagen, the major connective tissue protein in animals, possesses numerous characteristics not seen in synthetic polymers. Characteristics of collagen often cited include good compatibility with living tissue, promotion of cell growth, and absorption and assimilation of implantations. Natural collagen fibers, however, are not very useful in their native form due to intermolecular crosslinking, insolubility, rigid triple-helical structure, and immunogenicity.
Various methods and materials have been proposed for modifying collagen to render it more suitable as a biomedical adhesive. “In many instances, the prior modified collagen-based adhesives suffer from various deficiencies which include crosslinking/polymerization reactions that generate exothermic heat, long reaction times, and reactions that are inoperative in the presence of oxygen and physiological pH ranges. Moreover, many of the prior art modified collagen-based adhesives contain toxic materials, hence rendering them unsuitable for biomedical use.”
Another problem with collagen and other protein-based adhesives is the ability to form bond strengths and film strengths sufficient for the various uses to which such adhesives may be applicable. For example, U.S. Pat. No. 3,438,374 discloses a general matrix as a bioadhesive. Although the material was useful in some applications, the material did not work very well or failed in applications where the material was subjected to substantial pressures or was used to fill a substantial gap in tissue (as opposed to adhering two pieces of tissue together). For example, the adhesive was found not to be effective in sealing divided bronchial stumps (which is characterized by large gaps in tissue) and also was not effective in sealing blood vessels (which involve elevated fluid flow at high pressures).
A more recent advance in the field is the use of collagen monomers derivatized with an acylating agent or a sulphonating agent and polymerized with an appropriate polymerization initiator such as a chemical oxidant, ultraviolet irradiation, a suitable oxidative enzyme or atmospheric oxygen. These materials were shown to be biologically compatible, and their use was proposed for a number of biological applications. In particular, it was disclosed that these materials be used as adhesives to hold two tissues together or to hold a synthetic lenticule to an eye. They also were disclosed as useful in the formation of flexible films which could be used as a lap following surgery to prevent adhesion, as a synthetic tympanic membrane, as a substitute facial tissue, and as a wound dressing component. It was stated that the adhesive also may be used to seal an incision following cataract removal. The material was not proposed for use in sealing fluid leaks in a tissue that is a conduit and in particular in a tissue that is exposed to pulsating and elevated pressures in situ.
SUMMARY OF THE INVENTION
The invention provides methods and products for sealing a fluid leak in a tissue. The various methods and products permit one or more of the following advantages: (1) the ability to seal quickly, in some instances under 30 seconds; (2) the ability to be immediately exposed to elevated pressures of at least 50 mm Hg, and in some instances, above 125 and even above 250 mm Hg; (3) the ability to be immediately exposed to pulsating fluid upon sealing, particularly at high pressures; (4) the ability to plug substantial gaps in tissue, as opposed to adhesively binding tissues in contact with one another, to one another; and (5) the ability to seal body fluids in bodily conduits.
According to one aspect of the invention, a method for sealing a fluid leak in a tissue is provided. A polymerizable protein is applied to the tissue to form a covering for an opening in the tissue, which opening creates a fluid leak in the tissue. The covering then is exposed to a initiator so as to polymerize the covering in situ, so as to attach the covering to the tissue and so as to seal the opening from fluid leakage. The invention is useful in connection with sealing anastomoses and suture lines for blood vessels. The invention also is useful for scaling airholes in lung injuries, including injuries to parenchymal and bronchiole tissue (especially bronchiole stumps). The foregoing are examples of tissues that act as conduits for fluid which pulses through the conduits at elevated pressures. The invention also is useful in connection with sealing leakage in the bladder, repairing leakage in the bowel, and repairing leaks in dura mater.
According to some embodiments of the invention, the polymerization can be carried out in less than 3 minutes. In certain embodiments, the polymerization preferably is carried out in less than 30 seconds, more preferably between about 10 and 30 seconds and most preferably in about 15 seconds.
In other embodiments, the polymerizable protein is a viscous fluid, and the polymerization is carried out at between a pH of 6.0-9.0, more preferably 7.8-8.8, and most preferably between about 8.2 and 8.5. In still other embodiments, the polymerizable protein is in a solvent which includes an initiator. In these embodiments, the initiator can be sodium persulfate, sodium thiosulfate, ferrouschloride tetrahydrate, sodium bisulfate or an oxidative enzyme. Most preferably the initiator is sodium persulfate, and the sodium persulfate is present in the solvent collagen mixture in a range of 0.01M to 0.2M. Preferably, the initiator is a photochemical initiator. It is preferred that the irradiation used to initiate polymerization is a light band having a wavelength between about 250 and 550 nm.
In certain embodiments, the polymerizable protein is selected from the group consisting of collagen, albumin, gelatin, elastin, and fibrinogen. In certain embodiments the protein is derivatized with an agent that enhances the solubility of the protein under physiological conditions. In preferred embodiments, the polymerizable protein is collagen derivatized with an acylating agent and/or a sulfonating agent.
In other embodiments the method also includes the step of applying a primer to the tissue surface prior to applying the polymerizable protein to the tissue. The primer enhances the strength of the tissue seal. In a preferred embodiment the primer is a dilute solution of collagen having a concentration of 1-10 mg/ml. In a preferred embodiment the concentration of the dilute collagen solution is 4-8 mg/ml. In another embodiment the primer has a pH of 6.0-9.0. In a preferred embodiment the pH is 8.2-8.5.
According to another aspect of the invention, a method for sealing a fluid leak in a tissue is provided. A primer is applied to the tissue to form a primer layer and then a polymerizable protein is applied to the primer layer to form a covering for an opening in the tissue, which opening creates a fluid leak in the tissue. The covering then is exposed to a initiator so as to polymerize the covering in situ, so as to attach the covering to th
DeVore Dale P.
Pachence James M.
Putnam Charles
Jackson Gary
Testa Hurwitz & Thibeault LLP
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