Surgery – Instruments – Sutureless closure
Reexamination Certificate
2000-09-29
2003-02-25
Izaguirre, Ismael (Department: 3765)
Surgery
Instruments
Sutureless closure
Reexamination Certificate
active
06524327
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to synthetic surgical adhesives/sealants and tissue bonds created by reacting the adhesive with living in-situ tissue. More specifically, a unique tissue cross-linked polyurea-urethane bond is formed by reaction of isocyanate capped ethylene oxide diols, triols or polyols with activated living tissue.
2. Prior Art
Numerous urethane forming polyisocyanate reactions have been published, not all of them teach use as a surgical adhesive. Those that do teach use as a surgical adhesive do not teach the unique hydrogel/tissue bond formed in the present invention.
U.S. Pat. No. 4,994,542 (Matsuda et al) discloses a flexible surgical adhesive comprised of a NCO-terminated hydrophilic urethane prepolymer derived from a fluorine-containing polyisocyanate used alone or in combination with an unsaturated cyano compound. The high reactivity of fluorine-containing polyisocyanate capped urethane prepolymer with water makes it unlikely that such adhesives bond directly with untreated tissue. The addition of cyano compounds further increases the intra-polymer reactivity. These adhesives provide a mechanical bond by infiltrating fissures in the tissue rather than bonding directly to the nitrogenous groups of biological tissue. They consequently produce weaker bonds.
U.S. Pat. No. 5,173,301 (Itoh et al) discloses a NCO-terminated hydrophilic urethane prepolymer derived from an organic polyisocyanate and a polyol component comprising a polyester polyol derived from an electron-attracting group capable of being easily hydrolyzed within a living body. The present invention is not hydrolyzed in the body.
U.S. Pat. No. 4,743,632 (Marinovic) discloses a purified diisocyanate polyetherurethane prepolymer and polymers prepared by mixing the prepolymer with an organic filler to produce a space filling sealant. The purified preparations teach that each mole of diisocyanate prepolymer is substantially matched with one mole of a chain-extending compound. The purification process ensures no excess of isocyanate, and therefore the reaction proceeds slowly and only weakly bonds tissue.
U.S. Pat. No. 5,266,608 (Katz et al) discloses a non-elastomeric adhesive for bonding to calcified tissues. The present invention teaches an elastomeric adhesive.
U.S. Pat. No. 4,804,691 (English et al) discloses an adhesive comprised of a hydroxyl-terminated polyester reacted with 8 to 76 weight percent excess aromatic diisocyanate. The polyester-base polymer is degraded by the body.
U.S. Pat. No. 5,922,809 (Bhat et al) discloses an adhesive comprised of a polyisocyanate, polymers having isocyanate-reactive moieties, and a triol dispersion. The triol dispersion is not taught in the present invention.
As can be seen, many polyurethane prepolymer compositions have been patented. Some are strongly water reactive systems and tend to crosslink internally rather than with tissue. The resulting mechanical bond adheres to tissue, although it does not produce a chemical bond with cellular constituents. These bonds are weaker than those derived in the present invention, and are insufficient for general tissue adhesive use.
In addition, cure time is an important consideration in tissue adhesive formulation. Optimal cure time is less than 1 minute. Although fluorine-containing isocyanates are purported to be faster reacting, they still depend on diffusion of water into the prepolymer to be activated. Pre-mixing the prepolymer with water or providing a hygroscopic component to the prepolymer has not been taught. Tissue activation and rapid water uptake into the prepolymer are essential to achieve fast cures that bond tissue chemically.
Finally, an important feature of a surgical adhesive is biocompatibility. Those adhesives that attain strong adhesive properties use excess quantities of polyisocyanates. Unreacted polyisocyanates present toxicity risks. The present invention teaches a reactive wash to eliminate residual isocyanate activity. Additionally, a high oxyethylene content is important to achieve a fully hydrated tissue bond that resists chronic protein adsorption and denaturation. Continued protein denaturation can provoke a chronic inflammatory response in the body.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a chemical bond to living tissue that is biocompatible, elastomeric, and superior in strength.
It is another object of this invention to provide an adhesive combination for surgery having shortened cure time.
It is another object of this invention to provide an adhesive combination of lower toxicity to tissue.
The tissue bond of this invention is achieved by cross linking to living tissue and reacting the activated tissue with a pre-mixed aqueous solution of a high molecular weight ethylene oxide polyol or diol end-capped with an organic polyisocyanate.
It is one primary object of this invention to provide a surgical adhesive that is easily applied, cures quickly, and produces a strong tissue bond. The preparations disclosed here are liquids and can be stored at normal hospital room temperatures, and possess long shelf life.
It is a further object of this invention to provide a surgical adhesive that forms a stable polyurethane tissue bond that is inactivated before wound closure.
The invention thus comprises an organic hydrogel bond comprised of living tissue pre-treated with hydrogen peroxide, body derived fluids, at least one NCO-terminated hydrophilic urethane prepolymer, derived from an organic polyisocyanate and oxyethylene-based diols, triols or polyols comprised essentially all of hydroxyl groups capped with polyisocyanate. Substantially all of the prepolymer units are aliphatic or aromatic isocyanate-capped oxyethylene-based diols, triols or polyols. The molecular weight of the diols, triols or polyols prior to capping with polyisocyanate is at least 3,000. The polyisocyanate may be a toluene diisocyanate. The polyisocyanate may be isophorone diisocyanate. The polyisocyanate may be a mixture of xylene diisocyanate and 6-chloro 2,4,5-trifluoro-1,3 phenylene diisocyanate. The polyisocyanate may be a mixture of xylene diisocyanate and tetrafluoro-1,3-phenylene diisocyanate. The polyisocyanate may be a mixture of diphenylmethane diisocyanate and 6-chloro 2,4,5-trifluoro-1,3 phenylene diisocyanate. The polyisocyanate may be a mixture of diphenylmethane diisocyanate and tetrafluoro-1,3-phenylene diisocyanate. The polyisocyanate may be paraphenylene diisocyanate. The diols, triols or polyols are capped with polyisocyanate such that isocyanate-to-hydroxyl group ratio is between 1.5 and 2.5. The isocyanate concentration in the prepolymer units is preferably between 0.05 and 0.8 milliequivalents per gram. The organic hydrogel bond may further comprise a surfactant to control foam density. The organic hydrogel bond may further comprise hydroxyethylcellulose. The organic hydrogel bond may further comprise hydroxypropyl-cellulose.
The invention in a further descriptive embodiment preferably comprises a tissue crosslinked hydrophilic hydrated bond prepared by reacting together tissue, body derived fluids and a prepolymer in a prepolymer-to-water ratio of 3:1 to 20:1, the prepolymer prepared by: selecting diols, triols or polyols, substantially all of which are oxyethylene-based diols, triols or polyols having an average molecular weight of 3,000 to about 15,000, and reacting the diols, triols or polyols with an aliphatic or aromatic polyisocyanate at an isocyanate-to-hydroxyl ratio of about 1.5 to 2.5 so that all of the hydroyl groups of the diols, triols or polyols are capped with polyisocyanate and the resulting prepolymer has an isocyanate concentration of no more than 0.8 milliequivalents per gram. Preferably substantially all of the diols, triols or polyols selected in (a) are oxyethylene-based. Preferably the diols, triols and polyols of step (a) are dissolved in an organic solvent selected from acetonitrile or acetone. The hydrated bond may further preferably comprise non-body derived water, ideally saline solution c
Halgren Don
Izaguirre Ismael
Praxis, LLC
LandOfFree
In-situ bonds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with In-situ bonds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and In-situ bonds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3182015