FIELD OF THE INVENTION This invention relates to medical devices, particularly medical devices adapted to pass through narrow body vessels such as catheters which have an outer surface polymeric substrate having coated thereon a coating of such nature and sufficiently low thickness that the resulting coated medical device has high hoop tensile strength and good puncture resistance (durability).

BACKGROUND OF THE INVENTION Catheters are placed at various locations within a patient for a wide variety of purposes and medical procedures. For example, one type of catheter is a balloon dilatation catheter which is used in the treatment of a vascular stenosis.

Such a catheter has a balloon at its distal end which is intended to be placed, in a deflated condition, within the stenosis, and then inflated while in the stenosis to expand radially the stenosed lumen of the blood vessel. Typically, the placement of such catheters involves the use of a guidewire which may be advanced through the patient's vasculature to the location which is to be treated. The catheter, which has a guidewire lumen adapted to receive the guidewire, then is advanced over the wire to the stenosis, or, alternatively, the wire and catheter may be advanced in unison to the stenosis with the wire protruding from the distal end of the catheter.

It has long been known that hydrophilic coatings with low friction (coefficient of friction of 0.3 or less) are useful for a variety of medical devices such

as catheters, catheter introducers and the like. When low friction coating surfaces are applied to the substrate of such medical devices, such devices when introduced into the body slide easily within arteries, veins and other body orifices and passageways.

Examples of prior art catheters which have been provided with a lubricious coating in the manner referred to in the foregoing paragraph are coated catheters disclosed in U.S. Elton Patent No. 5,077,352, U.S. Elton Patent No. 5,160,790, U.S. Opolski Patent No. 5,272,012 and U.S. Rowland Patent No. 5,041,100.

While a number of prior art medical catheters possess high hoop tensile strength they are lacking in a sufficiently high enough puncture resistance.

By the present invention, a medical device, e.g., a catheter having a coating of such nature on its outer surface substrate is provided whereby the medical device has a puncture resistance greater than its uncoated form without affecting hoop tensile strength which results in an improved catheter of improved durability.

DESCRIPTION OF THE INVENTION It is an object of this invention to provide a medical device, e.g., a medical catheter made of a polymeric material which has been coated with a coating of such nature and applied in such a manner that the puncture resistance of the medical device (durability) has been increased while not decreasing any desirable physical property like hoop tensile strength nor significantly increasing the diameter of the product.

Another object of the invention is to obtain a medical catheter composed of a polymeric material having a coating wherein the resulting coated catheter is composed of materials of such characteristics, morphology and thickness that said coated catheter has a desirable combination of properties, including a high hoop tensile strength and acceptable puncture resistance.

It has been found that the objects of this invention may be realized by applying to the outer polymeric surface of a medical device, e.g., a medical catheter, and in particular, the inflatable balloon portion of the catheter, a polymeric coating of such nature and of sufficient thickness to obtain an improved puncture resistance

over that of the uncoated parent substrate so as to impart greater durability to the coated medical device over the parent uncoated medical device.

Suitable methods for applying the polymeric coating to the substrate surface of the catheter include dipping, painting, spraying or wiping the coating on the catheter outer surface substrate. Dipping is a preferred method as it allows for more control over the coating process. The thickness of the coatings is typically less than about 1 mil. A thickness range of about 0.02 to about 0.5 mils is more preferred. Thickness ranges of about 0.05 to about .25 mils and about 0. 1 to about 0.25 mils are also preferred.

Examples of suitable coating compositions are solutions or dispersions of polyurethane, acrylic polymers and epoxy resin materials in a suitable solvent or liquid carrier. For example, it has been surprisingly found that commercial polyurethane coatings such as Helmsman Urethane Coating or Carver Tripp Clear Polyurethane, commercial acrylic polymers such as Thompson's Minwax Polyacrylic Finish or commercial epoxy resins such as Hardman EpoWeldX can be used. It is noted that these commercial products may contain additives such as coloring which are unnecessary for practicing this invention. The basic building blocks of polyurethanes are are isocyanates containing two or more isocyanate groups and polyols containing two or more hydroxyl functions. Toluenediisocyanate, polymeric diphenylmethanediisocyanate, monomeric 4,4'-diphenylmethanediisocyanate, 1,6- hexamethylene diisocyanate and isophorone diisocyanate are common isocyanates that can be used either individually or as a mixture to produce polyurethanes for use in this invention. Polyurethanes are classified according to the polyol used. The polyols are generally polyethers and polyesters. Polyether-based urethanes are more resistant to hydrolysis and have higher resilience, good energy-absorption characteristics, good hysteresis characteristics, and good all-around chemical resistance. A polyester-based material will generally be stiffer and will have higher compression and tensile moduli, higher tear strength and cut resistance, higher operating temperature, lower compression set, and optimum abrasion resistance.

Castor-oil-based potting compounds are also convenient to use. CasChem markets a

family of polyurethane systems based on ricinoleate polyols derived from castor oil.

Diamines are the best general purpose curing agents for polyurethanes. Non-limiting examples of suitable acrylic polymers are those made up of methyl acrylate, ethyl acrylate or methyl methacrylate acrylic-esters. Other examples include the use of copolymers of methyl methacrylate with other monomers such as methyl and ethyl acrylate, acrylonitrile and styrene. Non-limiting examples of suitable epoxy resin materials are those based on the reaction of bisphenol A and epichlorohydrin in the presence of an alkaline catalyst, novolac epoxies such as cresols, and cycloaliphatics.

Epoxy resins can be cured with cross-linking agents or catalysts to develop desirable properties. Additional information on the production and use of polyurethane, acrylic polymer and epoxy resin can be found in the Modern Plastics Encyclopedia, October 1986, Volume 63, Number 10A, published by McGraw Hill, New York, NY and references therein or the Handbook of Plastics, Elastomers, and Composites, Third Ed., by Charles A. Harper, published 1996 by McGraw Hill, New York, NY and references therein. The preparation of the coatings can be a multi-step process.

Non-limiting examples of suitable solvents or carriers are water, aliphatic or aromatic hydrocarbons, heterocyclic aromatics, ethers, amines, amides, ketones, esters, halogenated aliphatic or aromatic hydrocarbons, sulfides, sulfoxides and the like. If the coating composition employs a curable material, the curable material is cured after evaporation of the liquid solvent or carrier of the coating composition after the coating solution has been applied to the substrate.

After applying the coating solution or dispersion, the solvent or liquid carrier is preferably allowed to evaporate from the coated substrate often by exposure to ambient conditions for from about 10 to about 180 minutes but can be evaporated at temperatures of from about 35° F to about 400" F for time periods of a few seconds to overnight depending upon the selection of solvent or liquid carrier and the speed with which evaporation is desired.

The organic balloon substrate that can be coated with a suitable coating for obtaining a coated catheter with high hoop tensile strength and acceptable

puncture resistance in accordance with this invention include nylon, polyether block amide, polyethylene terephthalate (PET), polyetherurethane, polyesterurethane, natural rubber, rubber latex, synthetic rubbers, polyester-polyether copolymers, ethylene methacrylic acid di-and inter polymers containing metal salts, polyethers, polyesters, and other polyurethanes, polycarbonates, polytetramethylene glycol ether urethane, and other organic materials including polyvinylchloride and other vinyl polymers, polyethylene and the like, as well as blends and alloys of the above.

Some of these materials are available under the trademarks such as Pebax available from Atochem, Inc. of Glen Rock, New Jersey, Mylar available from E.I. duPont deNemours and Co. of Wilmington, Delaware, Texin 985A from Mobay Corporation of Pittsburgh, Pennsylvania, Surlyn available from E.I. duPont deNemours and Co. of Wilmington, Delaware, Pellethane available from Dow Chemical of Midland, Michigan, and Lexan available from General Electric Company of Pittsfield, Massachusetts.

The balloons are preferably made from nylon, PET or blends or alloys thereof. It is desired that the hoop tensile strength or Hoop Stress of the balloons (uncoated and after coating to enhance durability) be about 10,000 psi or greater. It is more preferred that such balloons have a hoop tensile strength of about 25,000 psi or greater. The size of the balloons typically is in the range of about 0.5 to about 25 mm in diameter. More preferably the balloons range from about 1 to about 18 mm in diameter and most preferably from about 1 to about 4 mm in diameter. The balloons are typically biaxially orientated, but the use of other forms is also useful in the practice of this invention. The uncoated double wall thickness (DWT) of the balloon is typically from about 0.25 to about 3 mils thick. An uncoated DWT of about 0.5 to about 1.2 mils is more preferred.

All publications, patents and articles referred to herein are expressly incorporated herein in toto by reference thereto. The following examples are presented to illustrate the present invention but are in no way to be construed as limitations on the scope of the invention. It will be recognized by those skilled in the art that numerous changes and substitutions may be made without departing from the

spirit and purview of the invention.

EXAMPLE 1 Coatings Coating A Coating A is a solvent based polyurethane coating. The coating was prepared by dissolving Helmsman Urethane Coating in toluene. The dilution ratio of polyurethane to solvent was from about 1:2 to about 1:10 depending on the thickness of the coating desired.

Coating B Coating B is a water soluble polyurethane coating. The coating was prepared by dissolving Carver Tripp Clear Polyurethane in water. The dilution ratio of polyurethane to water was about 1:1 to about 1:10 depending on the thickness of the coating desired.

Coating C Coating C is a water soluble acrylic polymer coating. The coating was prepared by dissolving Thompson's Minwax Polyacrylic Finish in water. The dilution ratio of polyacrylic to water was about 1:1 to about 1:10 depending on the thickness of the coating desired.

Coating D Coating D is a solvent based polyurethane coating. The coating was prepared as follows. Initially, Cellulose Acetate Butyrate (1.8 g), e.g., Eastman Cellulose Acetate Butyrate 500-5 available from Eastman Chemical Company, Kingsport, Tennessee was combined with 16.2 g N-Butyl Acetate available from Van Waters & Rogers Incorporated, San Mateo, California. The solution was mixed for

approximately 24 hours on a paint roller or until all of the Cellulose Acetate Butyrate was dissolved. When dissolved, polyisocyanate (45.5 g), e.g., Mondur CB-60 PMA available from Miles Corporation, Pittsburgh, Pennsylvania, castor oil (35.0 g), e.g., DB Castor Oil available from CasChem, Incorporated, Bayonne, New Jersey, an additional 116.9 g N-Butyl Acetate available from Van Waters & Rogers Incorporated, San Mateo, California, 122.4 g of iso-Butyl Acetate available from Van Waters & Rogers Incorporated, San Mateo, California and 5.5 g Mineral Spirits available from Van Waters & Rogers Incorporated, San Mateo, California were added.

In addition, the components listed above can be varied to achieve different coating characteristics. Cellulose Acetate Butyrate can be used in the range of about 0.02 to about 2% with a preferred range being about 0.03 to about 0.68%.

N-Butyl Acetate can be used in the range of about 0. 1 to about 10% with a preferred range being about 0.2 to about 6.5%. The polyisocyanate can be used in the range of about 0.5 to about 22% with a preferred range being about 0.7 to about 18%.

The castor oil can be used in the range of about 0.4 to about 14.5% with a preferred range being about 0.5 to about 14%. Additional N-Butyl Acetate can be used in the range of about 24 to about 54% with a preferred range being about 30 to about 45 %.

iso-Butyl Acetate can be used in the range of about 24 to about 60% with a preferred range being about 30 to about 50%. All percentages are weight/weight.

Table 1 shows variations of coating D that were made and applied to balloons.

Table 1. Various Compositions of Coating D. Components W X Y Z Mondur CB-60 2.85g 8.47g 13.27g 17.61g Butyl/Iso-Butyl Acetete 92.91g 81.52g 71.44g 61.89g DB Castor Oil 2.24g 6.69g 10.24g 13.87g CAB Solon. 1.65g 3.67g 5.34g 6.82g 'Stock Butyl/Iso-Butyl Acetate solution was made by mixing Butyl Acetate (363.27 g), Iso-

Butyl Acetate (381.58 g) and mineral spirits (19.32 g) in a clear bottle and rolling until homogeneous.

2Stock CAB solution was made by mixing Cellulose Ester (28.21 g) and Butyl Acetate (253.65 g) in a clear bottle and rolling for 24 hours.

Table 2 shows balloons dipped in the various formulations of coating D shown in Table 1. The burst pressure and hence the hoop tensile strength of the coated balloons was determined and compared to similar balloons that were not coated. The results show that the coatings of this invention do not reduce the hoop tensile strength of balloons.

Table 2. Hoop tensile Strength of Catheters with Coating D Balloon Coating # of Dips Burst Pressure (bar) Al W 1 30.97 B1 X 1 27.84 B2 X 2 26.04 C1 1 Y 1 27.84 C2 Y 2 29.06 Dl z 1 24.06 D2 1- Z 2 31.04 Uncoated -- -- 29.02 Uncoated -- -- 26.07 Coating E Coating E is a solvent based epoxy resin coating. Hardman Epoxy Part A (2.5 g) and Hardman Epoxy Part B (2.4 g) both available as Hardman EpoweldX 8173 from Elementis Performance Polymers, Belleville NJ were dissolved in toluene (4.9 g) to produce a 50% solution of solids. Serial dilutions were performed to produce coating solutions of 33%, 25% and 20% solids. Balloons were single dipped immediately after mixing.

Balloons were coated with coating E as outlined in Table 3 below.

The burst pressure and hence the hoop tensile strength of the balloons coated with coating E was determined. The hoop tensile strength of the coated balloons was then compared to similar, uncoated balloons. The results show that the coatings of this invention do not reduce the hoop tensile strength of balloons.

Table 3. Hoop Tensile Strength of Balloons with Coating E Balloon Balloon Coated With # of Dips Burst Pressure (bar) A 50% solids 1 21.80 B 33% solids 1 20.99 C 25% solids 1 20.51 D 20% solids 1 20.65 E Uncoated -- 20.78 F Uncoated -- 19.98 Polyurethane Coatings A polyol (170 g), e.g., Desmophen A 405A, available from Bayer Corp. Pittsburgh, PA, a polyisocyanate (44 g), e.g., Modur CB-60 PMA, available from Bayer Corp., and acetone (2014 g) can be mixed to produce a polyurethane coating. The polyol can be used in the range of about 2 to about 15%, with the preferred range being about 5 to about 10%. The polyisocyanate can be used in the range of about 0.5 to about 10%, with the preferred range being about 1 to about 5%. Acetone can be used in the range of about 80 to about 99%, with the preferred range being about 85 to about 95 %.

Acrylic Polymer Coatings An acrylic polymer (4 g), e.g., PMMA HI 835S, available from LG Chemical, is dissolved in tetrahydrofuran (96 g) available from Aldrich. Acrylic polymers like PMMA HI 835S can be used in the range of about 0.1 to about 25% with the preferred range being about 0.5 to about 10%.

Epoxy Resin Coatings An epoxy resin (60 g), e.g., Epon 828 Bis A Epoxy Resin, available from Shell Chemical, an acrylate modifier (25 g), e.g., M-Cure 200 Acrylate Modifier, available from Sartomer, and an acrylate modifier (15 g), e.g., M-Cure 202 Acrylate Modifier, available from Sartomer, is mixed to produce part A of the epoxy resin. An amine (6 g), e.g., EpiCure 3005 Amidoamine, available from Shell Chemical, and a second amine (16 g), e.g., Ancamine 1638 Aliphatic Amine is mixed together to produce part B of the epoxy resin. Epoxy resins, e.g., Epon 828 Bis A Epoxy Resin can be used in the range of about 45 to about 75% with the preferred range being about 48 to about 72%. Modifiers, e.g., M-Cure 200 Acrylate Modifier can be used in the range of about 18 to about 32% with the preferred range being about 22.5 to about 27%. Modifiers, e.g., M-Cure 202 Acrylate Modifier can be used in the range of about 11 to about 19% with the preferred range being about 13 to about 17%. Amines, e.g., EpiCure 3005 Amidoamine can be used in the range of about 4 to about 8% with the preferred range being about 5 to about 7%. Amines, e.g., Ancamine 1638 Aliphatic Amine can be used in the range of about 12 to about 20% with the preferred range being about 14 to about 18%. Equal parts of part A and part B can dissolved in two parts toluene. The mixture can then be serially diluted to produce coating mixtures.

A high durometer coating can be made as follows. Two epoxy resins, e.g., AboCast 8-8 (100 g), available from Abatron, Kenosha, WI, AboCure 8-8 (100 g), available from Abatron, can be combined with toluene (100 g) to produce an epoxy coating. Typically the resins can be used in equal portions and toluene can be used in the range of about 10 to about 95%, with a preferred range being about 25 to about 75%.

EXAMPLE 2 Dipping Procedure Dipping is the preferred method of coating because the thickness of

the coat is more uniform and easier to control compared to other methods. For example, when coating a PET balloon, the balloon was first cleaned with acetone, isopropyl alcohol or the like. The balloon was then inflated to from about 2 to about 4 bars pressure and dipped into the coating mixture. Factors that affect the coating thickness and adhesion properties were the speed at which the article was introduced into and withdrawn from the mixture, the dwell time in the mixture and the number of times dipped into the coating mixture. The dwell time was found to influence the extent to which the coating was imbibed into the article surface. The down speed (inches/minute) can be over the range of about 1 to about 200 with a preferred range being about 40 to about 140. The dwell (seconds) time has no limit but typically is about 2 to about 40. The withdrawal rate (inches/minute) can be over the range of about 1 to about 200 with a preferred range being about 40 to about 140.

Typically, the double wall thickness of each balloon is first measured.

The balloon is then cleaned with isopropyl alcohol, acetone or similar solvent and heat sealed at each end with about 2 to about 4 bars pressure inside the balloon. The ballon is dipped, distal end first, into the coating solution. After removal from the coating solution, the balloon is air-dried. For multiple dipping, the balloon was allowed to air-dry for 20 minutes between dips. The balloons were then placed in a drying oven to cure. After curring, the balloons were removed and the double wall thickness measured.

EXAMPLE 3 Durability Testing Balloons were examined for durability using the following procedures.

The device used for testing was specifically designed for balloon catheters and to represent the environment the balloon catheters are typically used in. The device consists of a series of stainless steel sleeves with internal diameters that match the balloon's nominal outer diameter (OD). A balloon's nominal OD is defined as the outer diameter of the balloon after it has been pressurized from the collapsed

position to the inflated position that is free of wrinkles (normally pressures are from about 50 to about 125 psi). Each sleeve has one screw ground to a 60° included taper down to a 0.0065 inch diameter flat. The screw can be extended 0.011 inches toward the center of the cylinder. The sleeve was placed in a submersible fixture and the deflated balloon loaded into the sleeve. The screw was adjusted to a length of 0.011 inches and the apparatus submerged into a body temperature water bath. The balloon catheter was attached to an inflation device i.e., burst machine and inflated to either 12 or 16 bars. If the balloon did not burst, it was deflated and reinflated repeatedly until the balloon burst. The table below compares coating thickness, DWT, inflation pressure and durability between similar, coated and uncoated balloons.

Table 4. Durability of Coatings A, B, C, D and E. Coating r Inflation Durability Coating DWT1 Thickness (mil) Pressure Cycles (Avg)2 None 0.5 12 None 0.9 16 Coating A 1.4 0.45 12 4 Coating A 1.1 0.10 12 8 Coating B 1.2 0.15 12 59 Coating B 0.8 0.15 12 >73 Coating B 0.6 0.05 16 3 Coating C 1.2 0.35 12 32 Coating C 1.2 0.35 16 74 Coating C 1.5 0.30 12 76 Coating C 0.9 0.20 16 10 Coating C 0.8 0.15 16 20 Coating C 0.7 0.10 16 5 Coating C 0.6 0.05 16 1 Coating D 0.9 0.02 16 1 t Coating D 1.1 0.03 16 27 Coating D 1.0 0.05 16 8 Coating D 1.2 0.09 16 32 Coating D 1.1 0.10 16 12 Coating D 1.1 0.11 16 7 Coating D 1.3 0.21 16 6 Coating E 1.4 0.35 16 12 Coating E 0.9 0.13 16 19 Coating E 0.8 0.09 16 2 w Coating E 0.8 0.06 16 8 'Double wall thickness (DWT) is a measure of the thickness of the coating plus the wall thickness of the balloon catheter when the balloon is laid flat and both walls and the coating is measured.

2Durability is measured by cyclically inflating the balloon catheter to a certain pressure in a 3.0 mm sleeve against a 0.011" pin.

3The uncoated balloons burst during the first inflation.

Durability is defined as a coated balloon attaining at least one more cycle in the above-described test than a similar, uncoated balloon. A more preferred durability is greater than about 5 cycles more than an uncoated balloon and a most preferred durability is greater than about 10 cycles. A preferred range of durability is about 5 to about 50 cycles and a more preferred range is about 10 to about 20 cycles. Typically the testing is done from about 12 bar to about 16 bar which is the working pressure of the balloon. The testing can be done at pressures ranging from about the nominal pressure of the balloon to about the busting pressure of the balloon.

EXAMPLE 4 A length of PET balloon tubing was dipped into polyurethane solution D. It was then allowed to air dry approximately 20 minutes, followed by baking at 1200 F for 480 minutes. The coated tube was then formed into a balloon. The resulting product was a balloon catheter with durability (as measured by cyclic penetrations with a pointed probe to measure puncture resistance) greater than a catheter without above coating.

EXAMPLE 5 Hoop Tensile Strength Testing Hoop tensile strength also known as Hoop Stress was determined as follows. A balloon at body temperature was attached to a burst machine and inflated to the point at which the balloon ruptures. The Hoop Stress was then calculated by the following equation: HS = (Force @ Break (psi)) (Balloon Diameter) 2(Wall Thickness) For example, the Hoop Stress of a balloon of 3 mm diameter with a wall thickness of 0.0005 inches that ruptures at 20 bar is calculated as follows: HS = (20 bar) (14.7 psi/bar) (3.0 mm/25.4 mm/in) 2(0.0005 in) which calculates as a Hoop Stress of 34,720 psi.