Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Compositions to be polymerized by wave energy wherein said...
Reexamination Certificate
2000-07-14
2002-05-14
Nutter, Nathan M. (Department: 1711)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Compositions to be polymerized by wave energy wherein said...
C522S185000, C424S487000, C602S904000, C523S111000, C523S114000, C523S118000
Reexamination Certificate
active
06387977
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to methods and compositions for improving the adherence of polymer gels to surfaces, especially tissue surfaces; devices for applying the compositions and gels; and general methods for sealing surfaces with gels for therapeutic benefit.
Locally polymerized gels have been used as barriers and drug delivery devices for several medical conditions. Adherence of the formed gel to the tissue can be a problem, especially under surgical conditions, where the tissue surface to be treated is typically wet, and may further be covered with blood, mucus or other secretions. Hubbell and co-workers have described two methods for photopolymerizing gels in contact with tissue surfaces. In U.S. Pat. No. 5,410,016, hereby incorporated by reference, application of biodegradable macromers to tissue, followed by photopolymerization to form a gel, is described. Two methods for photopolymerizing gels are described. In “bulk” polymerization, a suitable photoinitiator and accessory reagents are solubilized or dispersed in a solution of gelling macromers. On application of light, the entire solution volume crosslinks to form a gel which acts as a local barrier or drug depot. These gels have substantial adherence to most surfaces, including tissue surfaces which are merely moist. However, if a confounding layer of fluid is present on the surface when the macromer/initiator solution is applied, then the gel may delaminate from the surface after its formation.
An alternative way of form a gel layer on a surface, as also described in U.S. Ser. No. 08/024,657, which is hereby incorporated by reference, is called the “interfacial” method. In this method, the surface to be coated is treated with a photoinitiator which adsorbs or absorbs to the surface. After washing away excess, unabsorbed photoinitiator, a polymerizable macromer solution is applied to the surface. On exposure to light, polymerization is initiated at the surface, and progresses outward into the solution to the limit of diffusion of the photoinitiator-generated radicals during their lifespan. Coating thicknesses of up to about 500 micrometers (microns) are routinely obtained. Since they are in effect “grown” from the tissue surface, such gel layers have excellent adhesion to the tissue surface under difficult conditions, including the presence of thin layers of fluid adherent to the surface. The limited thickness of such interfacial gels is desirable in some circumstances, but represents a major limitation where gels of substantially greater thickness than 500 microns are required, for example, for use in drug delivery, or in forming an effective barrier between the tissue surface and its surroundings.
In addition to the photopolymerizable gels described by Hubbell et al (WO 93/17669) and Sawhney et al, (
J. Biomed. Mats. Res.
28, 831-838, 1994), systems for forming drug delivery depots or barriers on surfaces include the polymers described in U.S. Pat. No. 4,938,763 to Dunn, et al., U.S. Pat. Nos. 5,100,992 and 4,826,945 to Cohn et al, U.S. Pat. Nos. 4,741,872 and 5,160,745 to De Luca et al, and U.S. Pat. No. 4,511,478 to Nowinski et al. Use of preformed barrier materials such as Goretex™ membrane (W. L.Gore) has been described in the literature.
Although all of these materials are suitable for application to tissue and other substrates, adhesion is in many cases limited, or in the case of the preformed barrier materials, essentially non-existent.
It is therefore an object of the present invention to provide methods and compositions for enhancing the adhesion of polymeric materials to tissue surfaces and other substrates.
It is a further object of the present invention to provide methods and compositions for increasing the thicknesses of polymeric materials which can be “tethered” to a tissue surface or other substrates.
It is a further object of the present invention to provide improved initiator systems for the formation of gels on tissues and other surfaces.
It is a further object of the present invention to provide improved methods and new medical indications for the sealing and coating of tissue.
It is a further object of the present invention to provide devices suitable for performing these operations.
SUMMARY OF THE INVENTION
An improved barrier, coating or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. In the preferred embodiment, tissue is stained with a photoinitiator, then the polymer solution or gel in combination with a defined amount of the same or a different photoinitator is applied to the tissue. On exposure to light, the resulting system polymerizes at the surface, giving excellent adherence, and also forms a gel throughout the illuminated volume. Thus a gel barrier or coating of arbitrary thickness can be applied to a surface while maintaining high adherence at the interface. This process is referred to herein as “priming”. The polymerizable barrier materials are highly useful for sealing tissue surfaces and junctions against leaks of fluids. In the examples described below, the fluids are air and blood; however, the principle is also applicable to other fluids, including bowel contents, urine, bile, cerebrospinal fluid, vitreous and aqueous humors and other fluids whose migration within a living organism must be contained.
In another embodiment, “priming” can be used to reliably adhere preformed barriers or coatings to tissue or other surfaces, or to adhere tissue surfaces to each other. A first surface and a preformed barrier or coating, or another surface, are prestained with initiator, and a thin layer of polymerizable monomer containing initiator is placed between them. Strong adhesion is obtained between the two surfaces on polymerization of the monomer. In a similar fashion, tissue surfaces can be adhered to each other in repair of wounds and formation of anastomoses.
The priming method is suitable for any mode of polymerization. While especially effective in photopolymerization, chemical or thermal polymerization can also be accomplished by this method. Further, an enhancement of photoinitiation can be achieved by adding suitable redox initiation components to the system, providing a new form of light-controlled chemically accelerated polymerization reaction, especially effective in the presence of blood.
According to one embodiment, the invention provides a device for dispensing a fluid to a tissue surface in a medical setting, having a proximal portion operable by a user of the device and a distal portion having an applicator outlet for addressing the tissue surface. The devices is characterized in that it includes at least two chambers for receiving fluids to be dispensed to the tissue surface and conduits connecting each chamber to an applicator outlet at the distal portion of the device. The device also includes an optical emitter at the distal portion for applying light to the fluid at the tissue surface.
According to another embodiment, the invention provides a device for dispensing a fluid to a tissue surface as described above, characterized in that it includes at least two chambers for receiving fluids to be dispensed to the tissue surface and conduits connecting each chamber to an applicator outlet at the distal portion of the device, a first dispensing mechanism activating dispensing of fluid from the first chamber to the tissue surface, operably linkable to a trigger at the proximal portion, and a second dispensing mechanism activating dispensing of fluid from the second chamber to the tissue surface, operably linkable to a trigger at the proximal portion.
According to another embodiment, the invention provides a dispensing adapter for use in a medical setting. The adapter operates by attachment to a device having a reservoir for containing a fluid to be dispensed to a tissue surface and a fluid outlet, and is characterized in that it is fastenable to the device and removable therefrom, and includes a conduit having a proximal end connectable in a fluid
Avila Luis Z.
Barman Shikha P.
Bromander Thomas S.
Coury Arthur J.
Elbert Donald L.
Focal, Inc.
Holland & Knight LLP
Nutter Nathan M.
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