Surgery – Instruments – Sutureless closure
Reexamination Certificate
1999-09-29
2001-05-01
Thaler, Michael H. (Department: 3731)
Surgery
Instruments
Sutureless closure
Reexamination Certificate
active
06224622
ABSTRACT:
BACKGROUND
1. Field of the Invention
This invention relates to cyanoacrylate tissue adhesives, and more particularly, to bioabsorbable cyanoacrylate tissue adhesive compositions and to methods for making and using these compositions. The compositions are useful in medical applications, including, but not limited to, wound and surgical incision closure, medical device fixation, sealants and void fillers, embolic agents and other general medical applications.
2. Description of the Background
Surgical incisions and wounds may be closed by three general methods, suturing, stapling and adhesive bonding.
U.S. Pat. No. 5,578,046 notes that sutures are bioabsorbable when the material that they are made from is capable of being broken down into smaller constituents, which can be metabolized and excreted by the living organism. Such materials are useful for temporarily holding tissues in a desired position during healing and are absorbed by the organism after a period of time. U.S. Pat. No. 5,578,046 as well as the patents and literature in turn referenced by U.S. Pat. No. 5,578,046 are incorporated herein by reference.
Wound suturing has the advantage of producing bioabsorbable, non-toxic degradation products. However, it also has disadvantages. Suturing requires time and skill. It causes additional trauma to the tissue by piercing and does not provide a hermetic closure.
Cyanoacrylates posses the unique property to bond living tissue. They have been widely and successfully tested for closing wounds and incisions, especially in cases where suturing does not provide satisfactory results. See Lijoi A. et al, “Subacute left ventricular free wall rupture complicating acute myocardial infarction. Successful surgical repair with a sutureless technique”, J. Cardiovascular Surgery, 1996 December, 37(6), 627-630; Tebala G. D. et al, “The use of cyanoacrylate tissue adhesive in high-risk intestinal anastomoses”, Surgery Today, 1995, 25 (12), 1069-72 and Zaki I. et al, “Split skin grafting on severely damaged skin. A technique using absorbable tissue adhesive”, J. of Dermatologic Surgery and Oncology, 1994 December, 20(12), 827-9.
Cyanoacrylate tissue adhesives have the following advantages over suturing: they save time; they can bond difficult to suture tissues; they can provide a hermetic closure; they have hemostatic action; they produce better cosmetic results; and they may be indispensable in emergencies.
A major disadvantage of cyanoacrylate adhesives is that one of the degradation products is formaldehyde, which is toxic to the surrounding tissues (see Pani K. C. et al, “The degradation of n-butyl alpha-cyanoacrylate tissue adhesive. II.”, Surgery, 1968 March, 63(3), 481-9). For this reason, cyanoacrylates have not found favor with the FDA for internal tissue closure. Only topical skin closure applications have been FDA approved.
Other disadvantages of cyanoacrylate tissue adhesives are their runniness (low viscosity) in uncured form and stiffness when cured.
SUMMARY OF THE INVENTION
The present invention overcomes the problems and disadvantages associated with current cyanoacrylate adhesives and provides compositions useful as bioabsorbable tissue adhesives. The adhesives of the present invention are quickly biodegradable with reduced formaldehyde generation, and provide hermetic closure and hemostatic action. Additional benefits include increased application viscosity and increased flexibility in the cured state of the adhesives.
One embodiment of the invention is directed to a copolymer derived from one or more cyanoacrylates and one or more other monomers, wherein the one or more cyanoacrylates are selected from the group consisting of alkyl 2-cyanoacrylate, alkenyl 2-cyanoacrylate, alkoxyalkyl 2-cyanoacrylate, and carbalkoxyalkyl 2-cyanoacrylate. The alkyl group of the one or more cyanoacrylates preferably has 1 to 16 carbon atoms, and the one or more other monomers are selected from the group consisting of glycolide, lactide, &egr;-caprolactone, dioxanone and trimethylene carbonate.
Another embodiment is directed to a method for making a bioabsorbable tissue adhesive composition comprising the step of dissolving the above described copolymers into a cyanoacrylate monomer or blend of cyanoacrylate monomers. The cyanoacrylate monomer or monomers are selected from the group consisting of alkyl 2-cyanoacrylate, alkenyl 2-cyanoacrylate, alkoxyalkyl 2-cyanoacrylate, or carbalkoxyalkyl 2-cyanoacrylate. The alkyl group of the cyanoacrylate monomer or monomers preferably has 1 to 16 carbon atoms.
Another embodiment is directed to bioabsorbable tissue adhesives made by this method.
Another embodiment of the invention is directed to a method for making a bioabsorbable tissue adhesive composition comprising the step of dissolving one or more copolymers, the copolymers derived from glycolide and two other monomers, into a cyanoacrylate monomer or blend of cyanoacrylate monomers. The one or more copolymers possess amorphous structure and are in a rubbery state at body temperature. The two other monomers are selected from the group consisting of lactide, &egr;-caprolactone, dioxanone and trimethylene carbonate. The cyanoacrylate monomer or monomers are selected from the group consisting of alkyl 2-cyanoacrylate, alkenyl 2-cyanoacrylate, alkoxyalkyl 2-cyanoacrylate, or carbalkoxyalkyl 2-cyanoacrylate. The alkyl group of the cyanoacrylate monomer or monomers preferably has 1 to 16 carbon atoms.
Another embodiment is directed to bioabsorbable tissue adhesives made by this method.
Other embodiments and advantages of the invention are set forth in part in the description which follows, and in part, will be obvious from this description, or may be learned from the practice of the invention.
DESCRIPTION OF THE INVENTION
As embodied and broadly described herein, the present invention is directed to cyanoacrylate-based tissue adhesives which combine the advantages of bioabsorbable suturing with the advantages of adhesive bonding. The compositions of the present invention are quickly biodegradable with reduced formaldehyde generation, and provide hermetic closure and hemostatic action. Additional benefits of the present invention include increased application viscosity and increased flexibility in the cured state of the adhesives.
The present invention is useful in medical applications, including veterinary and other applications where a biodegradable bond is desired. Compositions of the invention may be used to bond tissue to tissue, tissue to a foreign object such as an implant, or even two foreign objects to each other.
Although lactide—&egr;-caprolactone copolymers have been added to cyanoacrylate for thickening and plasticizing of the resultant polymer with good experimental results (see Tseng Y.-C. et al, “Physical modification of a-cyanoacrylate for application as surgical adhesives”, Progress in Biomedical Polymers, Ed. By C. G. Gebelein and R. L. Dunn, Plenum Press, New York, 1990, pp. 53-63), the lactide—&egr;-caprolactone copolymer is not as easily biodegradable as glycolide-based copolymers and not easily soluble into cyanoacrylate at high concentrations.
In contrast, the present invention provides for an adhesive bond with enhanced biodegradability.
One embodiment of the present invention utilizes novel biodegradable copolymers derived from cyanoacrylate and one or more of the following monomers: glycolide, lactide, &egr;-caprolactone, dioxanone, and trimethylene carbonate. The cyanoacrylate moiety of the novel copolymers renders them easily soluble in a wide range of proportions into cyanoacrylate monomers, yielding adhesives with high viscosity in uncured state and high flexibility in cured state. The adhesives have an enhanced bioabsorbability profile with non-toxic degradation products and a reduced amount of formaldehyde.
The present invention includes two different types of copolymers as modifiers for cyanoacrylate.
One class is a series of terpolymers derived from glycolide and two or more of the following monomers: lactide, &egr;-caprolactone, dioxanone, and trimethylene carbonate. The
Brobeck Phleger & Harrison LLP
Chemence, Inc.
Thaler Michael H.
Trinh (Vikki) Hoa B.
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