WO1996040305A1

WO1996040305A1 - Fluid treated transparent polytetrafluoroethylene product

Info

Publication number: WO1996040305A1
Application number: PCT/US1996/005510
Authority: WO
Inventors: Terry A. Hubbard
Original assignee: W.L. Gore & Associates, Inc.
Priority date: 1995-06-07
Filing date: 1996-04-19
Publication date: 1996-12-19
Also published as: AU5561296A

Abstract

A method for improving the ultrasonic transparency of a porous polytetrafluoroethylene (PTFE) material which is implanted in a living body. The method involves impregnation of the material with a fluid such as saline, glycerol or a saccharide solution to displace air in the microstructure of the material rendering it transparent. This facilitates ultrasonic imaging particularly with the first several weeks after implantation.

Description

FLUID TREΞATED TRANSPARENT POLYTETRAFLUOROETHYLENE

PRODUCT

Field of the Invention

The present invention broadly relates to porous membrane materials which are produced from porous polytetrafluoroethylene (PTFE). Specifically, the invention relates to a membrane barrier for protecting and isolating an internal organ or body tissue from surrounding organs or tissue which barrier is porous PTFE or more preferably porous expanded PTFE, which has been treated with fluid to render the membrane barrier at least partially transparent to permit visual or ultrasonic examination of organs and tissue behind the barrier.

Background of the Invention

Formation of adhesions on body tissues and organs is a major medical problem. Adhesions are scar tissue that bind anatomical surfaces which surfaces are normally separated from one another. Adhesions are often found in the abdominal area where they occur after surgery or form due to inflammation or injury. Adhesions may cause abdominal pain, nausea, vomiting and distention. In some cases, a corrective surgery procedure as an adhesiotomy is necessary to remove adhesions.

In view of the various medical problems that may result from formation of adhesions, medical science has been investigating various methods to prevent adhesions. These methods have included the use of liquid adjuncts which include Dextran^", derivatives of cellulose, lactated Ringer's solution and drug therapy in the form of topical antibiotics and nonsteroid anti-inflammatories. Use of biologic and synthetic barriers such as amnion, mesentery, peritoneal grafts, preserved bovine pericardium, allograft and xenograft dura matter have been proposed. Most of these barriers have not proven to be effective in preventing adhesions. Presently there are two barrier adjuncts that have been demonstrated to be effective in the peritoneal cavity which barriers are oxidized regenerated cellulose (OR) and expanded polytetrafluoroethylene (ePTFE). The former has proven to be ineffective in the presence of all but exacting hemostasis and may, in fact, be adhesiogenic due to its acidic nature and the foreign body response it engenders. On the other hand, barriers of ePTFE have been used in many clinical conditions as ePTFE is one of the most inert biomaterials known. ePTFE has been clinically used for many years and has a unique configuration which is flexible, porous, chemically inert and has been effective as an adhesion barrier for such applications as pericardial membrane substitutes, dura matter substitute or as a wrap for autograft vessels.

A number of techniques have been employed in the prior art to improve the patency of synthetic vascular prosthesis fabricated from biomaterials such as expanded PTFE. As indicated, PTFE is one of the most widely used of the vascular graft materials. However, most of the techniques utilized to improve the patency of such materials has involved applying a coating such as a polymer coating to achieve desired techniques. Reference is made to European Patent Application Publication No. 0261470.

Other publications such as International Publication No. W09221715 suggest that the properties of expanded PTFE may be created or improved by treating the PTFE with a fluorinated organic polymer fluid either before or after expansion. The resulting treated porous PTFE has enhanced resistance to degradation by radiation and enhanced fine particle filtration which make it highly suited for applications such as outdoor clothing, filters, mechanical seals and vascular grafts.

Other treatments are suggested for improving the resistance of ePTFE barriers to thrombosis and infection which treatments extract trapped gas from the biomaterials. These processes, generally known as priming techniques, exclude air from a material and include application of a vacuum and carbon dioxide exposure as well as saline, degas saline, ethanol and acetone soaking. See U.S. Patent No. 5,181 ,903 for a detailed discussion of such priming techniques.

Thus, while the prior art is replete with various suggestions for treating or improving the characteristics of ePTFE for certain specialized applications, particularly medical applications, none of the prior references extant suggest the treatment of ePTFE to render it transparent prior to its application. Generally ePTFE is opaque and its opaqueness is a major drawback in many medical applications. For example, in the case of pediatric cardiac surgery, it is imperative that the patient's heart be ultrasonically imaged immediately after the procedure. In the case of endoscopic surgery, transparency of ePTFE allows the surgeon to image organs and tissue beneath the ePTFE. The reduced reflectance reduces the video flaring that normally occurs when the endoscope illumination is reflected into the video camera. These are only several instances in which use of a transparent ePTFE barrier would be beneficial to attending physicians. It is known that surgical membranes, such as those of expanded ePTFE, once wetted in sjtu after implantation with proteinaceous, aqueous fluids may turn translucent after some time, normally more than two weeks.

Summary of the Invention The invention involves the impregnation of ePTFE prior to implantation with a variety of fluids for the purpose of rendering the ePTFE optically and ultrasonically transparent. The process involves the impregnation of the ePTFE at low pressures, below 500 psig. Various impregnating fluids may be used including normal saline, glycerol solutions and saccharide solutions. Optimal clarity is obtained by matching the index and refraction of the impregnating solution to that of the ePTFE material. Since most of the ePTFE materials consist of a mixture of crystalline and amorphous domains, the index and refraction of the impregnating solution may be adjusted to obtain optimal clarity of the ePTFE material. The resulting transparent material is provided in suitable sterile form in a package of polypropylene or similar packaging material and contained in a solution such as saline to maintain the material wetted and transparent. The wetting solution may be selected from a wide variety of solutions other than saline, preferably having a lower vapor pressure than water which will maintain the barrier in the wetted condition.

A protective barrier according to the present invention is fabricated from a biocompatible material which is preferably a microporous membrane with a pore size of less than about 5 microns. A preferred material is porous expanded PTFE such as Gore-Tex® Cardiovascular Patch or Gore-Tex® Preclude (formerly surgical membrane), both available from W.L. Gore & Associates,

Flagstaff, Arizona. Porous, expanded PTFE is a preferred material because of the variety of microstructures that are possible and its inert characteristic. In general, porous expanded PTFE made in accordance with the teachings of U.S. Patent Nos. 3,953,566 and 4,187,390 is preferred. This material has a microstructure that can be generally characterized as having nodes connected by fibrils. The porosity of porous expanded PTFE is characterized in terms of fibril length. The fibril length of porous expanded PTFE that has been expanded in a single direction is defined herein as the average of ten measurements between nodes and connected by fibrils in the direction of expansion. Ten measurements are made in the following manner: First, a photomicrograph is made of a representative portion of the sample surface having sufficient magnification to show at least five sequential fibrils within the length of the photomicrograph. Two parallel lines are drawn across the length of the photomicrograph so as to divide the photograph into three equal areas with the lines being drawn in the direction of expansion and parallel to the direction of orientation of the fibrils. Measuring from left to right, five measurements of fibril length are made along the top line in the photograph beginning with the first node to intersect the line near the left edge of the photograph and continuing with consecutive nodes intersecting the line. Five more measurements are made along the other line from right to left, beginning with the first node, to intersect the line on the right side of the photograph. The ten measurements obtained by this method are averaged to obtain the fibril length of the material. For a porous, expanded PTFE material that has been expanded in more than one direction, the fibril length is estimated by examining a representative scanning electron photomicrograph of the material surface and comparing fibril lengths as described above in a manner that represents the various directional orientation of the fibrils.

Detailed Discussion of the Preferred Embodiment(s)

Reference will now be made in detail to a preferred embodiment of the present invention. The invention comprises a barrier of expanded PTFE for implantation which is impregnated with a fluid which renders the ePTFE visibly and ultrasonically transparent. PTFE, which has been expanded, due to its structural and chemical characteristics, is widely used as an adhesion barrier but is normally a white, opaque material. The term "transparent" as used herein is to be understood to include partial light passing characteristics and also includes translucent.

To improve the biomaterial's characteristics making it more susceptible to ultrasonic imaging and visual and optical inspection, the invention contemplates the impregnation of ePTFE with a variety of fluids under application of pressure which results in the interstitial spaces of the porous microstructure being filled with the fluid displacing air within the microstructure. When hydrostatic or fluid compression pressure is applied to the barrier material submerged within the impregnating fluid, the air within the interstitial spaces is diffused and displaced by a liquid in which the material is submerged transferring the material from opaque to translucent.

Various fluids may be suitably utilized as the impregnating fluid including a wide range of biocompatible fluids or solutions such as normal saline, glycerol, and saccharide solutions. Preferably the impregnating solution will have an index of refraction which approximately matches that of PTFE which is approximately 3.375. Most ePTFE materials consist of a mixture of crystalline amorphous domains. The index of the refraction of the impregnating solution may be adjusted or selected to obtain optimal clarity of the resulting barrier. The impregnating solution may also include an appropriate therapeutic agent. Therapeutic agents may consist of antithrobogenics such as Heparin which limit fibrin deposition. Anti-viral or anti-bacterial agents (antibiotics) which eliminate, alleviate or increase resistance to infections as well as to other modalities may also be included in the impregnating solution.

Incorporation of therapeutics in and on the biomaterial is beneficial as incorporation of such therapeutics may lessen the problems associated with use of the material including thrombogenesis and infection.

The ePTFE barrier material preferably has a thickness of less than one millimeter with a thickness of about 0.1 mm being preferred. The barrier material is in the form of a membrane having a porosity of less than 5 microns with 1 micron being preferred. The material is nominally worked to expand the material to achieve the characteristics set forth above.

The objects and advantages of the invention are further illustrated by the following examples, but the particular materials, quantities and other parameters recited in the example, as well as other conditions, are exemplary only and should not be construed to unduly limit the invention.

Example In accordance with the present invention, expanded PTFE material having a thickness of about 0.1 mm and a porosity of about 1 micron is submerged in a fluid such as normal saline and subjected to hydrostatic pressure in a suitable hydrostatic chamber in the range of approximately 150 to 550 psig. The interstitial spaces in the material are initially filled with air and once placed under pressure the air is gradually displaced with the fluid. The air-filled spaces generally render the ePTFE initially opaque to ultrasonic image and to the visual light spectrum. The spaces occupied by the air are replaced by the liquid rendering the material generally transparent. A suitable impregnating fluid ideally has the following characteristics: (1) It is hydrophobic; and (2) has a compatible index of refraction. Suitable fluids include normal saline solutions, polysaccharides, gums and gels, glycerol and a 50/50 mixture with gum xanthan, sera with lipids. The barrier is subjected to treatment in a hydrostatic chamber for a time sufficient to denucleate the biomaterial by displacing or dissolving all or substantially all of the air and gases from the biomaterial with liquid. As a typical example, the barrier may be subjected to treatment in a hydrostatic pressure for four to five minutes at approximately 400 psi or for a longer period as for example 10 minutes at a lower pressure of approximately 200 psi.

Prior to treatment of the hydrostatic pressure, it may be desirable to subject the biomaterial to a partial vacuum as for example treatment in a vacuum chamber at about 760 mm pressure. Treatment in a partial vacuum results in degassing of the material and reduces the time and pressure required for treatment in the hydrostatic chamber.

After treatment, the barrier becomes transparent or substantially transparent permitting optical and ultrasonic inspection. The barrier material is then packaged in a suitable package such as polypropylene packaging or a composite package of a foil having a polypropylene insert or panel which is clear for visual inspection of the contents. The barrier is cut to the appropriate size and is placed in the package with a sufficient quantity of a preserving fluid such as saline or the impregnating fluid to maintain the barrier in a wetted condition. The packaging material should have a low permeability to water vapor and, as indicated, should be clear or at least have a clear panel or section to permit visual inspection of the contents. The package may be sterilized by conventional autoclaving techniques.

The resulting product is provided to the user ready for implantation, requiring only removal from the package and subsequent surgical application. The transparent barrier performs as a conventional ePTFE barrier for prevention of adhesions in such applications as abdominal, thoracic, hernia and atrial repairs. In addition to serving as an adhesion barrier, the transparency of the barrier permits the surgeon to visually inspect the tissue and organs behind the barrier and also facilitates ultrasonic and endoscopic imaging, particularly in the critical period within two weeks after surgery at a time when the membrane retains opaqueness and has not yet, due to normal in situ wetting, become translucent.

The method of the present invention involves initially degassing a biomaterial such as ePTFE in a partial vacuum. The material preferably has a thickness of less than 1 mm and has been nominally worked. After degassing, the barrier material is placed in a hydrostatic chamber immersed in a suitable solution. The treatment in the hydrostatic chamber occurs at a pressure of up to 500 psi and may take 10 minutes or more. By increasing the hydrostatic pressure, the time in which the material is required to be within the chamber for adequate impregnation and displacement of air and gases which cause opaqueness. As indicated, the solutions may be various solutions such as saline solution, polysaccharide, a gel, glycerol or sera with lipids. It is useful to select a fluid that is hydrophobic as it will be drawn more easily into the interstitial spaces of the barrier material. Another characteristic is that the liquid should have an index of refraction approximating that of the barrier material. The barrier once suitably impregnated and wetted may be packaged in a package which preferably has a transparent window so that the contents of the package can be viewed. The material is packaged in a wetted condition in the package in a preserving fluid. The material is then sterilized by conventional sterilization techniques such as autoclaving or gas sterilization methods. While the principles of the invention have been made clear in the illustrative embodiments set forth above, it will be obvious to those skilled in the art to make various modifications can be made to the barrier and process of the present invention. To the extent that these various modifications do not depart from the spirit and scope of the appended claims, they are intended to be encompassed therein. I CLAIM:

Claims

CLAIMS:

1. A method for improving the ultrasonic transparency of porous PTFE implantable/barrier material comprising treating the porous PTFE material with a fluid prior to implantation and at a predetermined hydrostatic pressure sufficient to displace the air in the microstructure with fluid to render the material substantially transparent.

2. The method of Claim 1 wherein said fluid is selected from a group consisting of saline solutions, glycerol solutions, gels, gel-forming sols and saccharide solutions.

3. The method of Claim 1 wherein said hydrostatic pressure is applied in a range of from about 100 to 550 psig.

4. The method of Claim 1 wherein said porous PTFE has a thickness of less than about one millimeter and a porosity of less than about 10 microns.

5. The method of Claim 1 wherein said fluid includes a therapeutic agent.

6. The method of Claim 1 wherein said fluid has an index of refraction substantially equivalent to porous PTFE.

7. The method of Claim 1 including the additional steps of packaging the fluid treated material in a wetted condition in a wetting fluid.

8. The method of Claim 7 wherein said wetting fluid is the same fluid as the impregnating fluid.

9. The method of Claim 1 wherein material is initially degassed prior to fluid treatment.

10. The method of Claim 1 wherein said package is a foil package with a transparent viewing area.

11. A porous membrane consisting essentially of a porous PTFE material which has been fluid treated to render it substantially transparent prior to implantation.

12. The membrane of Claim 11 wherein said material has been hydrostatically fluid treated at a pressure of from about 100 to 550 psig.

13. The membrane of Claim 11 wherein said membrane has a thickness of up to about 1 millimeter and a porosity of about up to 10 microns.

14. The membrane of Claim 11 wherein said membrane is packaged in a fluid in a wetted condition to maintain transparency.

15. A method of using a liquid impregnated, optically transparent sheet of porous polytetrafluoroethylene for enhancing the ultrasonic imaging of a portion of a living body comprising:

(a) providing a liquid impregnated, optically transparent section of porous polytetrafluoroethylene;

(b) implanting the said sections of porous polytetrafluoroethylene into the living body; and (c) ultrasonically imaging a portion of the living body through said sheet within a predetermined time period after implantation.

16. The method of Claim 15 wherein said sheet is implanted adjacent the pericardium.

17. The method of Claim 15 wherein said predetermined time period is less than about two weeks.

18. The method of Claim 15 wherein said section of porous polytetrafluoroethylene is provided for use in sterile packaging.