HK1085642B - Apparatus for preventing adhesions between an implant and surrounding tissues - Google Patents

Description

Device for preventing adhesion between an implant and surrounding tissue

Technical Field

The present invention relates generally to medical devices, and more particularly to methods and apparatus for reducing post-operative adhesion between living tissue and an implant introduced into a surgical site of a patient.

Background

A major clinical problem associated with surgical procedures or inflammation may be unwanted tissue growth or adhesion, which may occur in the initial stages of the healing process following surgery or conditions. Another problem is foreign body reaction in response to medical devices or implants introduced into the surgical site. Yet another problem is leakage, migration, or diffusion of substances, such as fluids, from the implant into the surrounding tissue.

One approach to solving the adhesion problem is to use a bioresorbable barrier material in the form of a gel, coating, fabric, foam, film, or the like, disposed between the healing site and the adjacent surrounding tissue after surgery. Examples of such barrier materials are found in U.S. patent 5412068 to Tang et al, U.S. patent 5795584 to Totakura et al, U.S. patents 6034140 and 6133325 to Schwartz et al, and U.S. patent 6136333 to Cohn et al, all of which are incorporated herein by reference.

More specifically, the U.S. patent to Tang et al discloses films and other bioresorbable medical devices made from polycarbonate fibers. The U.S. patent to Totakura et al discloses a surgical adhesion barrier comprising a copolymer and/or block copolymer derived from trimethylene carbonate. U.S. patent to Schwartz et al discloses an anti-adhesive film made of a carboxyl group containing polysaccharide and a polyether. The U.S. patent to Cohn et al discloses anti-adhesion polymeric compositions comprising poly (ester)/poly (alkylene oxide) ABA triblock or AB diblock. Similarly, the problem of foreign body reactions is addressed by applying biocompatible polymer coatings to medical devices such as vascular stents. One method for coating a vascular stent is disclosed in U.S. patent 6153252 to Hossainy et al, the contents of which are also incorporated herein by reference.

Disadvantageously, the coatings and other separators described above have been only marginally successful. For example, some prior art spacer materials are resorbed into the body too quickly, resulting in an undesirable local decrease in pH, which causes or exacerbates problems such as local inflammation, discomfort, and/or foreign antibody responses. Other materials require too long an absorption time, may be insufficiently malleable, or require complex chemical compositions and/or reactions that increase manufacturing costs.

Disclosure of Invention

New applications have been found for anti-adhesive film materials. More specifically, it has been found that the anti-adhesion membranes disclosed herein, in addition to serving as barriers between adjacent living tissue, may also be adapted to be disposed on an implant introduced into a surgical site of a patient in order to prevent unwanted reactions between the implant and surrounding tissue. The implant may be a biological implant, such as a transplanted organ, or may be a non-biological implant, such as a medical device implant. Among the devices to which the principles of the present invention apply are bone graft substitutes, bone cements, tissue adhesives and cements, bone fixation components (plates, meshes, screws, and rods), prosthetic prostheses, tissue augmentation devices (e.g., breast implants, penile implants, and collagen), pacemakers, defibrillators, eye balls, sutures, staples, staple fibers, cochlear implants, pumping devices, artificial organs, non-resorbable sheets and membranes, bone growth stimulators, neural stimulators, dental implants, guided tissue and guided bone regeneration membranes, eyelid weights, and tympanostomy tubes. The type of pellicle material used in any particular application will depend on the application and the characteristics of the surgical site to which the pellicle is being applied.

Of particular interest are resorbable microfilms or membranes disclosed in U.S. patent 09/805411, filed 3/12/2001, the contents of which are hereby incorporated by reference. In particular, the above-identified applications disclose scar tissue attenuating barrier membranes made entirely of resorbable polymers and configured to be absorbed into the body relatively slowly over time, for example, to reduce the negative side effects that may occur. In a preferred embodiment of the invention, the membrane material is selected from the group consisting of lactide polymers (e.g. copolymers) of two or more lactides. It has now been found that these polylactide membranes have an additional use, namely as protective barriers for use on foreign bodies such as implants.

Also of interest are the film forming techniques disclosed in U.S. provisional patent 60/399792, filed on 31/7/2002 and in U.S. provisional patent 60/408393, filed on 4/9/2002, the contents of which are incorporated herein by reference. Films made by these techniques have been found to be particularly effective for use on the foreign body implants disclosed herein.

In the method according to the invention, an anti-adhesive film is applied to the implant before the body of the implant is introduced into the surgical site of the patient. The implant comprises biological material, such as a transplanted organ, or non-biological material, such as a medical device implant. The film may be applied to the implant by various means. In one example, a membrane according to the present invention is shrink wrapped around an implant, such as a pacemaker. In another example, an implant, such as a breast implant, is spray coated with the thin film material disclosed herein.

Based on the description herein, the description of the specification, and the understanding of one of ordinary skill in the art, the features or combinations of features described herein are included within the scope of the present invention as long as the features included in any combination do not conflict with one another. Additional advantages and aspects of the invention will become better understood with reference to the following detailed description and claims.

Drawings

FIG. 1 is a schematic diagram of a method of coating a pacemaker according to one embodiment of the present invention; and

fig. 2 is a schematic view of a method of coating a breast implant according to another embodiment of the invention.

Detailed Description

Reference will now be made in detail to the preferred embodiments of the present invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same or similar reference numbers will be used throughout the drawings and the description to refer to the same or like parts. It should be noted that the drawings are drawn in a simplified manner and are not to precise scale. For the purposes of this disclosure, directional terminology, such as top, bottom, left, right, up, down, over, above, below, beneath, rear, and front, is used with reference to the accompanying drawings for simplicity and clarity. These directional terms should not be construed to limit the scope of the invention in any way.

Although described herein with reference to certain illustrated embodiments, it is to be understood that these embodiments are merely illustrative and not restrictive. Although the following detailed description refers to illustrated embodiments, it is intended that the description be construed to cover any variations, alterations, and equivalents of the embodiments, and fall within the spirit and scope of the invention as defined by the appended claims.

The present invention relates to a method of reducing post-operative adhesion between an implant and surrounding tissue at a surgical site, comprising applying and/or forming an anti-adhesion membrane on and around the implant. A device comprising the implant and the anti-adhesion membrane may then be placed in the patient at the surgical site.

The films of the present invention can be constructed from a variety of biodegradable materials, such as resorbable polymers. For example, the membrane material applied to or formed on the implant comprises a lactide polymer, such as a copolymer of two or more lactide monomers. In one embodiment, the membrane material is preferably selected from the group consisting of lactide polymers (e.g., copolymers) of two or more monomers. Non-limiting polymers useful for forming membranes of the present invention, according to one embodiment of the present invention, include polymers (e.g., copolymers) of lactide (L, D, DL, or combinations thereof), glycolide, trimethylene carbonate, caprolactone, and/or physical and chemical combinations thereof. In one embodiment, the membrane comprises polylactide, which may be a copolymer of L-lactide and D, L-lactide. For example, the copolymer may comprise about 60-80% L-lactide and about 20-40% D, L-lactide, and in a preferred embodiment, the copolymer comprises poly (L-lactide-co-D, L-lactide) 70: 30Resomer LR708 manufactured and supplied by Boehringer Ingelheim KG, Germany. It has been found that a membrane constructed from such a material can hinder or prevent tissue adhesion so as to reduce scarring and/or inflammation, and that the membrane can resorb within 24 months or less of implantation into a mammal.

In one embodiment, the membrane is formed from a polymer derived (e.g., a homopolymer and/or copolymer) from one or more cyclic esters, such as lactide (L, D, DL, or combinations thereof), epsilon-caprolactone, glycolide. For example, the film may include approximately 1-99% epsilon-caprolactone in one embodiment, or 20-40% epsilon-caprolactone in another embodiment. In one example, the membrane includes 65: 35 poly (L-lactide-co-epsilon-caprolactone). In other embodiments, butyrolactone, valerolactone, or dimethylpropanolide can be used with or as a replacement for epsilon-caprolactone. In another embodiment, the membrane comprises a copolymer comprising lactide and glycolide that can be resorbed into the body more rapidly than the poly (L-lactide-co-D, L-lactide) described above.

The anti-adhesion film of the present invention can be applied to a wide variety of foreign objects including, but not limited to, graft materials, transplanted organs, and medical devices, including medical devices surrounded by living tissue including, but not limited to, fascia, soft tissues, muscles, organs, fat, adipose, membranes, pericardium, plura, periostium, peritoneum, dura, intestines, ovaries, veins, arteries, epidermis, tendons, ligaments, nerves, bones, and cartilage. Graft materials include autograft materials, xenograft materials, allograft materials, and combinations thereof. Examples of suitable graft materials include veins, arteries, heart valves, skin, dermis, epidermis, nerves, tendons, ligaments, bone marrow, blood, leukocytes, erythrocytes, gonadal cells, embryos, cells, adipose, fat, muscle, cartilage, fascia, membranes, pericardium, plura, periostium, peritoneum, and dura. Implants may include transplanted organs such as kidneys, heart, eyes, and liver, among others.

Other implants include non-biological materials, such as medical devices. Examples of suitable non-biological implants include, but are not limited to, bone graft substitutes, bone cements, tissue adhesives and cements, bone fixation components, defibrillators, eyeballs, sutures, staples, cochlear implants, pumping devices, artificial organs, non-resorbable membranes, bone growth stimulators, neurostimulators, dental implants, guided tissue and guided bone regeneration membranes, eyelid weights, and tympanostomy tubes. Other medical devices may include prosthetic prostheses, such as fluid-filled prosthetic prostheses. One example of a fluid-filled prosthesis is a breast implant, such as a saline or silicone breast implant. Further, the medical device may comprise an electronic device, such as a pacemaker.

The film may be formed or applied to the implant or device using any of a variety of techniques including, but not limited to, wrapping, interweaving, layering, draping, tape wrapping, adjacent placement, side-by-side positioning, and sandwiching.

In a first embodiment of the invention, the anti-adhesion material is pre-formed as a thin film prior to application to the implant. In a second embodiment of the invention, the material is applied as a coating, which is dried to form a film or barrier around the implant. The coated film may be effective as a protective layer around the implant, and/or may be effective as a resorbable barrier, as described herein. FIG. 1 illustrates one method of applying a pre-formed film. Fig. 2 shows a method of forming a thin film by coating and drying. The material used to form the membrane in both figures may include, for example, poly (L-lactide-co-D, L-lactide). However, it should be understood that other bioresorbable polymers having anti-adhesion properties may be used in alternative embodiments. In other variant embodiments, even non-resorbable polymers or polymers without anti-adhesive properties may be used, depending on the application of the film. For example, the film or separator may include one or more portions that include a resorbable polymer and one or more portions that include a non-resorbable polymer.

Fig. 1 illustrates a method of applying a pre-formed membrane 10 to a medical device 11, such as a pacemaker 12. The pre-formed membrane 10 is preferably a non-porous membrane formed from a single layer of polylactide material adapted to maintain a smooth surfaced barrier between the implant and the surrounding tissue. More preferably, the material in its final shape has a viscosity characteristic, such as inherent viscosity, in the range of about 0.20-10.00g/dL in chloroform at 25 degrees Celsius. For many applications, the disclosed films have an optimized range of tack properties of about 1.00-3.00 g/dL. In one embodiment, the viscosity property is greater than 1g/dL, preferably greater than 2g/dL, and more preferably greater than about 3 g/dL. It is also highly preferred that the film have a thickness of less than about 300 microns, and more preferably in the range of about 10-100 microns. In a preferred embodiment, the thickness is in the range of about 10-50 microns. The thickness should be uniform in the axial and trans-axial directions except at the outermost edge of the film 10 where the thickness is 2-4 times the remainder of the film. The thickness margin may provide the film with increased adhesion strength and reduced risk of damage in, for example, adhesive applications.

It is recommended that film 10 be preformed by the extrusion and stretching techniques disclosed in U.S. provisional patents 60/399792 and 60/408393. However, other standard film forming processes may be used in alternate embodiments. For example, compression molding may be used, or any suitable technique, such as that disclosed in encyclopedia of Polymer Science and Engineering, Vol.12, p.204-210 (1988), the contents of which are incorporated herein by reference. However, due to the unusual thickness of the film 10, certain techniques such as injection molding may be inadequate and may not provide adequate performance. By using a specific manufacturing technique, multiple layers of polymer material can be formed in one film. The multilayer film may provide improved benefits and advantages, particularly when multiple resorbable materials are used, such as a first resorbable material that degrades at a first rate and a second resorbable material that degrades at a second rate.

After the forming process, the membrane 10 is placed over or under the pacemaker 12 and wrapped around the pacemaker 12 to substantially encapsulate the pacemaker. As shown in fig. 1, the pacemaker is fully encapsulated. For other implants, including pacemakers, the membrane 10 may be wrapped around a major portion of the implant, so that only a minor portion of the implant is in direct contact with the biological environment of the human or animal patient in which the implant is disposed. As shown in fig. 1, a blower 14 or other heating device is then used to raise the temperature of the film 10, which may be supported on a suitable frame or holder (not shown) to a temperature above the glass transition temperature. In the case of the preferred polylactide material, the glass transition temperature is approximately 55-60 degrees Celsius. When in the glass transition state, the film shrinks in a predetermined manner, depending on the process used to manufacture the film. For example, a film extruded uniaxially according to the process disclosed in the above-mentioned co-pending U.S. patent shrinks at about 3 times along one axis (the longitudinal axis in the preferred embodiment) and 10-15% along the transverse axis. In one embodiment, the biaxially extruded film shrinks substantially the same along both axes. After cooling back below the glass transition temperature, the film 10 hardens or sets into its new coating configuration 16. The coating configuration may include a membrane 10 tightly wrapped around the implant. In a particular embodiment, substantially all of the exposed surface of the implant is covered by the membrane. In another embodiment, the membrane is in direct contact with the surface of the implant. In other embodiments, the membrane is wrapped around the implant so that the membrane does not contact the implant surface, but rather substantially surrounds the implant. For example, the membrane may be configured as a bag that is wrapped around the implant, wherein a gas or liquid fills the space between the membrane and the implant. No adhesives or other securing structures or methods are required to hold the film 10 in its wrapped configuration. However, it is within the scope of the invention to mold the coated implant, such as pacemaker 12, or to apply cement or other adhesive to the corners of the membrane as an additional step as the coated implant is cooled and heated.

Heat shrinking is effective in applications such as implantation of a device or other implant into a surgical site of a patient, but not necessarily attached to an anatomical structure. In applications where the implant device or implant is attached to an anatomical structure or tissue, it is preferable to mechanically secure the pre-formed membrane to the device or implant and to the surrounding body or tissue. The techniques used include: such that the film is wrapped, interwoven, laminated, overlaid, tape wrapped, adjacently disposed, positioned side-by-side, and sandwiched with respect to the implant and the surrounding body or tissue. Sutures or sutures, for example, may also be used to attach the preformed membrane to the surrounding muscle. As another example, a preformed membrane may be secured to bone using resorbable bone screws or staples. In other cases, crimping or folding the film into an anatomical slit may be sufficient to facilitate securing in place. Adhesives such as fibrin sealant or resorbable cyanoacrylate adhesives may also be used to secure the preformed membrane, either alone or in combination with any of the other means of attachment described above. Alternatively, the preformed membrane may be heat bonded, such as by a bipolar electrocautery device, ultrasonically welded, or similarly sealed directly to the surrounding or adjacent body.

In certain applications, for example in the case of larger or irregularly shaped implants to be implanted, it is more practical to coat the implant than to apply a preformed film. For example, fig. 2 shows a method of spray coating a breast implant 18 in the form of an implant having saline in a silicone shell.

Preferably, the coating solution 20 is formed by dissolving a bioresorbable polymer, such as the poly (L-lactide-co-D, L-lactide) material described above, in a suitable solvent. The solvent may be selected from the group consisting of ethyl acetate, acetonitrile, acetone, Methyl Ethyl Ketone (MEK), Tetrahydrofuran (THF), picoline (pyrole), and any combination of two or more thereof. In one embodiment of the invention, the solution 20 has a concentration of about 0.1-5.0 weight percent of the bioresorbable polymer. The solution 20 is placed in a suitable spray 22, such as an ultrasonic spray unit, and sprayed as a fine particle mist onto the surface of the implant 18. Spraying of the solution may be carried out using any conventional propellant. For example, the solution may be sprayed using a pump or an aerosol-based spraying device. Can be fed under the atmospheric pressure conditionThe ejection is performed. After spraying, implant 18 is dried, preferably air dried for about 1-5 hours, to remove 80-90% of the solvent, and then placed with a spray of about 1X 10^-2In the vacuum oven 24 at a pressure of, for example, about 55 degrees celsius or less, to remove as much of the remaining solvent as possible. In the case of organic solvents, it is particularly important to keep only very little solvent, and preferably no solvent at all.

After the initial application of the coating, one or more additional coatings, in whole or in part, may be applied if desired. The coating need not be uniform in thickness, but the final thickness at the thinnest portion should be no less than 10 microns. Preferably, the final thickness in substantially all portions is in the range of about 10-300 microns, and more preferably in the range of about 10-50 microns. As described herein, providing multiple coatings of different thicknesses can help to selectively control the resorption rate of the separator film.

While the best modes for carrying out the invention have been described in detail, those familiar with the art to which this invention relates will recognize various alternative constructions and embodiments for practicing the invention without departing from the scope of the invention.

Claims (25)

1. An apparatus, comprising:

an implant configured to facilitate insertion into a surgical site of a patient surrounded by tissue, wherein the tissue surrounds and contacts substantially all of an outer surface of the device when the implant is inserted into the surgical site; and

a resorbable thin membrane surrounding the implant to reduce adhesion between the implant and the surrounding tissue, the resorbable thin membrane being disposed over substantially all of an outer surface of the implant.

2. The apparatus of claim 1, wherein the implant comprises a biological implant.

3. The apparatus of claim 2, wherein the biological implant comprises a transplanted organ.

4. The apparatus of claim 2, wherein the biological implant comprises a graft material.

5. The apparatus of claim 4, wherein the graft material is selected from the group consisting of autograft material, xenograft material, allograft material, and combinations thereof.

6. The device of claim 5, wherein the graft material is selected from the group consisting of veins, arteries, heart valves, skin, nerves, tendons, ligaments, bone marrow, blood, embryos, cells, fat, muscle, cartilage, fascia, membranes, pericardium, plura, periostium, peritoneum, and dura.

7. The apparatus of claim 5, wherein the graft material is selected from the group consisting of dermis, epidermis, bone, white blood cells, red blood cells, gonadal cells and adipose.

8. The device of claim 2, wherein the surrounding tissue is selected from the group consisting of fascia, muscle, fat, membrane, pericardium, plura, periostium, peritoneum, dura, intestine, ovary, vein, artery, epidermis, tendon, ligament, nerve, and bone.

9. The device of claim 2, wherein the surrounding tissue is selected from the group consisting of soft tissue, animal fat, intestinal tubing, and cartilage.

10. The device of claim 2, wherein the surrounding tissue is an organ.

11. The apparatus of claim 1, wherein the implant comprises a non-biological body.

12. The apparatus of claim 11, wherein the non-living body comprises a medical device selected from the group consisting of bone graft substitutes, bone cements, tissue adhesives and cements, bone fixation members, defibrillators, eyeballs, sutures, staples, cochlear implants, pumping devices, non-resorbable membranes, bone growth stimulators, neurostimulators, dental implants, guided tissue and guided bone regeneration membranes, eyelid weights, and tympanostomy tubes.

13. The apparatus of claim 11, wherein the non-living body comprises a medical device selected from the group consisting of a suture fiber and an artificial organ.

14. The device of claim 1, wherein the resorbable membrane comprises a heat-shrunk membrane disposed about the implant.

15. The device of claim 14, wherein the film comprises at least one layer of said resorbable polymer-based material.

16. The device of claim 15, wherein the film comprises a single layer of said resorbable polymer-based material.

17. A device as claimed in claim 16, wherein the single layer of resorbable polymer-based material has a thickness of 10-100 microns.

18. The device of claim 1, wherein the membrane comprises a substantially flat membrane having a first substantially smooth side and a second substantially smooth side.

19. The apparatus of claim 15, wherein the polymer-based material has a substantially uniform composition.

20. The apparatus of claim 19, wherein the polymer-based material is comprised of a material selected from the group consisting essentially of:

a lactide polymer; and

copolymers of two or more cyclic esters.

21. The apparatus of claim 11, wherein the non-living body comprises a fluid-filled implantable prosthesis.

22. The apparatus of claim 21, wherein the fluid-filled implantable repair prosthesis comprises a breast implant.

23. The apparatus of claim 22, wherein the breast implant comprises a saline type implant within a silicone housing.

24. The apparatus of claim 11, wherein the non-living organism comprises a pacemaker.

25. The apparatus of claim 19, wherein the polymer-based material is selected from the group consisting of:

a lactide polymer; and

copolymers of two or more lactides.