Compositions – Compositions containing a single chemical reactant or plural...
Reexamination Certificate
1999-10-29
2003-06-17
Medley, Margaret (Department: 1714)
Compositions
Compositions containing a single chemical reactant or plural...
C252S182180, C252S182190, C422S001000, C422S022000, C522S152000, C523S111000, C523S118000, C524S081000, C524S259000, C524S295000, C524S296000, C524S297000, C524S310000, C524S315000, C524S317000, C524S369000, C524S470000, C524S375000, C524S486000
Reexamination Certificate
active
06579469
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to monomer and polymer adhesive and sealant compositions, and to their production for industrial and medical uses.
2. State of the Art Monomer and polymer adhesives are used in both industrial (including household) and medical applications. Included among these adhesives are the 1,1-disubstituted ethylene monomers and polymers, such as the &agr;-cyanoacrylates. Since the discovery of the adhesive properties of such monomers and polymers, they have found wide use due to the speed with which they cure, the strength of the resulting bond formed, and their relative ease of use. These characteristics have made &agr;-cyanoacrylate adhesives the primary choice for numerous applications such as bonding plastics, rubbers, glass, metals, wood, and, more recently, biological tissues.
It is known that monomeric forms of &agr;-cyanoacrylates are extremely reactive, polymerizing rapidly in the presence of even minute amounts of an initiator, including moisture present in the air or on moist surfaces such as animal tissue. Monomers of &agr;-cyanoacrylates are anionically polymerizable or free radical polymerizable, or polymerizable by zwitterions or ion pairs to form polymers. Once polymerization has been initiated, the cure rate can be very rapid.
Medical applications of 1,1-disubstituted ethylene adhesive compositions include use as an alternate or an adjunct to surgical sutures and staples in wound closure as well as for covering and protecting surface wounds such as lacerations, abrasions, burns, stomatitis, sores, and other surface wounds. When an adhesive is applied, it is usually applied in its monomeric form, and the resultant polymerization gives rise to the desired adhesive bond.
For example, polymerizable 1,1-disubstituted ethylene monomers, and adhesive compositions comprising such monomers, are disclosed in U.S. Pat. No. 5,328,687 to Leung et al. Suitable methods for applying such compositions to substrates, and particularly in medical applications, are described in, for example, U.S. Pat. Nos. 5,582,834, 5,575,997, and 5,624,669, all to Leung et al.
It is known to use cyanoacrylate adhesives to deliver bioactive agents to a wound site. For example, the above patents to Leung et al. disclose such technology in some detail. Examples of such bioactive agents include antimicrobial agents to be released into the wound. U.S. Pat. Nos. 5,684,042; 5,753,699; 5,762,919; 5,783,177; 5,811,091; and 5,902,594, all to Greff et al., disclose that an antimicrobially effective amount of an antimicrobial agent may be incorporated into the polymerizable cyanoacrylate ester composition to promote wound healing and retard infection of the wound. See col. 2, lines 50-53 and Abstract of the '699 patent. In order to achieve an antimicrobial effect, an antimicrobial complex of iodine molecules with a biocompatible polymer is used. The iodine/polymer complexes are dispersible in the cyanoacrylate ester. See col. 7, lines 45-48 of the '699 patent. However, the iodine/polymer complexes were not soluble in the cyanoacrylate ester. See Table I, col. 12, line 55-col. 13, line 14 of the '699 patent. See also, U.S. Pat. Nos. 5,730,994 and 5,807,563 to Askill et al. and WO 99/18950 to Berger et al.
It is also important to prevent the introduction of microorganisms to the wound site during treatment of the wound. Cyanoacrylate compositions, at least those for use in medical applications, are generally initially sterile. That is, the compositions as manufactured do not contain live microorganisms. However, through improper handling of the compositions or repeated exposure of the compositions to a non-sterile environment, such as with multiple use applicators, microorganisms that are present in the air may be introduced into a cyanoacrylate composition and survive, resulting in the contamination of the composition. Although the source for this characteristic is not understood, it has been observed that cyanoacrylate compositions inherently possess some antimicrobial activity. In particular, cyanoacrylate compositions themselves prevent the growth of some types of microorganisms within the composition. However, cyanoacrylate compositions by themselves do not possess such a broad spectrum of antimicrobial activity that all amounts of every type of microorganisms would not grow in the compositions.
A way to inactivate microorganisms in the cyanoacrylate compositions is to sterilize the composition. However, sterilization of &agr;-cyanoacrylate adhesive compositions is often difficult to achieve. For example, widely practiced methods of sterilization, such as dry and moist heat sterilization, ionizing radiation, exposure to gas, and aseptic filtration, are not always convenient for use with monomeric cyanoacrylate compositions. Problems sometimes arise due to polymerization of the monomer during the sterilization process. In many cases, sterilization-induced polymerization is so severe that the resulting product is unusable.
Additionally, even if complete sterilization of cyanoacrylate compositions is achieved, such that all microorganisms present in the composition are destroyed, improper handling or exposure to air after sterilization could result in introduction and growth of microorganisms in the cyanoacrylate compositions.
Thus, a need exists for improved monomer cyanoacrylate adhesive compositions, especially for medical uses, wherein the growth of microorganisms in a cyanoacrylate composition is prevented and the performance of the adhesive composition is not compromised.
SUMMARY OF THE INVENTION
The present invention provides a monomeric adhesive composition comprising an antimicrobial preservative agent and a polymerizable alkyl cyanoacrylate monomer. In embodiments, the antimicrobial agent is soluble in the monomer at room temperature and the resultant composition is stable for at least a given amount of time. However, in some specific embodiments, complete solubility may not be required. Production of the composition includes mixing a polymerizable alkyl cyanoacrylate monomer and an antimicrobial agent in a container. The monomeric adhesive composition may be sterilized. Production of the sterilized composition includes placing a polymerizable alkyl cyanoacrylate monomer and an antimicrobial agent in a container, sealing the container and sterilizing the container and the mixture. Optionally, the container used to hold the composition in embodiments of the present invention can be a multi-use container or packaging system. The compositions produced, packaged and sterilized according to the present invention are stable, and have extended utility, as compared to adhesive compositions of the prior art.
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Badejo Ibraheem T.
Hedgpeth Daniel L.
Mainwaring Lawrence H.
Narang Upvan
Nicholson William S. C.
Closure Medical Corporation
Medley Margaret
Oliff & Berridg,e PLC
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