WO1996003164A1

WO1996003164A1 - Hydrophilic coating material for intracorporeal use

Info

Publication number: WO1996003164A1
Application number: PCT/US1995/009267
Authority: WO
Inventors: Eugene Michal
Original assignee: Advanced Cardiovascular Systems, Inc.
Priority date: 1994-07-22
Filing date: 1995-07-21
Publication date: 1996-02-08
Also published as: CA2195744A1; EP0772467A1; JP2000511946A

Abstract

A flexible hydrophilic coating on a device which is to contact body fluid and particularly for flexible substrates on intracorporeal devices such as balloons on dilatation catheters. The coating includes at least 30 % of a copolymer of a hydrophilic monomer and a plasticizer monomer. A presently preferred hydrophilic monomer is acrylamide and the presently preferred plasticizer monomer is methoxy (polyethylene glycol) mono methacrylate where the polyethylene glycol moiety has a molecular weight of about 1000. Other hydrophilic polymers, such as n-vinyl pyrrolidone, may also be incorporated into the coating. Both polymers are treated to attach latent photoactive groups to facilitate the bonding thereof to a substrate.

Description

HYDROPHILIC COATING MATERIAL FOR INTRACORPOREAL USE

BACKGROUND OF THE INVENTION This invention generally relates to intraluminal catheters, such as guiding catheters and balloon dilatation catheters used in percutaneous transluminal coronary angioplasty (PTCA).

In typical PTCA procedures, a guiding catheter having a preshaped distal tip is percutaneously introduced by a Seldinger technique into the cardiovascular system of a patient and advanced within the ■ system until the preshaped distal tip of the guiding catheter is disposed within the ascending aorta adjacent the ostium of the desired coronary artery. The guiding catheter is twisted or torqued from its proximal end, which extends outside the patient, to turn the distal tip of the guiding catheter so that it can be guided into the desired coronary ostium. A

balloon dilatation catheter are introduced into and advanced through the guiding catheter to the distal tip thereof out of the distal tip of the guiding catheter until the balloon on the distal extremity of the dilatation catheter is properly positioned across the lesion. Once properly positioned, the balloon is inflated to a predetermined size with radiopaque liquid at relatively high pressures {e.g., generally 4-12 atmospheres) to dilate the stenotic region of the diseased artery. One or more inflations may be necessary to effectively dilate the stenosis. Additional stenoses may be dilatated with the same catheter. When the dilatations are completed, the balloon is deflated so that the dilatation catheter can be removed from the dilated stenosis and normal blood flow will resume through the dilated artery.

There are several well known types of balloon dilatation catheters which are suitable for coronary angioplasty. They include conventional over-the-wire catheters, fixed-wire catheters, rapid exchange type catheters and perfusion type catheters. Lubricous coatings have been applied to the surfaces of guiding catheters, dilatation catheters and other intraluminal catheters in order to reduce the coefficient of friction of the surfaces of these catheters and to facilitate the advancement and withdrawal of these catheters through various body lumens. For example, silicone coatings have been applied to the exterior of various catheters in order to reduce the coefficient of friction of the catheter surface, but these coatings are frequently not very durable and lose substantial portions of their lubricity during an intraluminal or intravascular procedure. Durable, lubricous silicone coatings are described in copending application Serial No. 07/913,775, filed July 13, 1992, but the application of these lubricous coatings and linings described in the copending application are for the most part complicated manufacturing procedures.

What has been needed and heretofore unavailable is a durable coating for plastic surfaces having long lasting lubricity which does not require complicated manufacturing procedures. The present invention satisfies this and other needs.

SUMMARY OF THE INVENTION This invention is directed to an improved intracorporeal device, such as a catheter, having a durable, flexible coating which is

formed of hydrophilic material and which provides a low coefficient of friction when in contact with an aqueous based liquid.

The durable, flexible coating of the invention is generally formed at least in part from a copolymer product comprising a hydrophilic monomeric material and a plasticizing monomeric material. The copolymer product comprises at least about 50% of the hydrophilic monomer and from about 2% to about 50%, preferably about 5% to about 30%, of the plasticizing monomer. As used herein, all references to percent refer to percent by weight unless otherwise noted. The co- polymer is treated to attach latent photoactive groups to facilitate the bonding of the reacted copolymer to the desired substrate, as taught in U.S. Patent 5,002,582, which is incorporated herein by reference. Additional disclosures are found in U.S. Patent 4,722,906, U.S. Patent 4,973,493 and U.S. Patent 4,979,959 which are incorporated herein by reference. The coating formed is a durable, flexible hydrophilic coating. At least about 30%, preferably at least about 40%, of the coating should comprise the copolymer of the hydrophilic monomer and the plasticizing monomer. Other hydrophilic polymers may be incorporated into the coating to modify coating properties. The additional hydrophilic polymers should likewise be treated to attach latent photoactive groups as previously described.

The hydrophilic monomeric material forming the copolymer and the hydrophilic monomeric material forming any hydrophilic polymer incorporated into the coating with the copolymer are preferably selected from one or more hydrophilic monomers having the general formula

π^CH ⁼ CR2R3

where R₁ is a hydrogen or pyrrolidone, R₂ is a hydrogen or a methyl group,

R₃ is a hydrogen or -COR₄, and R₄ is -NH₂, -OH, -NHC(CH₃)₂CH₂CO_R5,

-N(CH₃)₂, -O(CH₂)_nOH, or -OCH₃CHCH₂OH, where R₅ is CH₃ or OH, and n is 1 or 2

Particularly suitable hydrophilic monomers include acrylamide and N-vinyl

pyrrolidone.

The plasticizer may be a hydrophilic plasticizing monomer and particularly a plasticizing monomer having the general formula CH₂ = CR₆-COO(CH₂CH₂O)-CH₂CH_OR₆ where R₆ is a hydrogen or methyl group and n is an integer from about 1 to about 25. A suitable hydrophilic plasticizing monomer may at least in part be selected from the group consisting of (methoxy)poly(ethylene glycol) monomethacrylate, poly.ethylene glycol) monomethacrylate,

(methoxy)poly(ethylene glycol) acrylate, poly(ethylene glycol) acryiate, having a molecular weight from about 500 to about 1500, and mixtures thereof.

The plasticizer material may also be at least in part a hydrophobic plasticizing monomer having the general structure

CH₂C = COOR₇ where R₇ is a straight chain or branched alkyl group having from 2 to 22 carbon atoms, and particularly is a plasticizing monomer selected from at least one of the

group consisting of 2-ethyl hexl acrylate, n-butyl acrylate and stearyl methacrylate.

The above mentioned plasticizing monomers are particularly suitable for use by incorporating with the hydrophilic monomer before the mixture is polymerized. It is sometimes desirable to partially polymerize the hydrophilic monomeric material, incorporate a water soluble, relatively non-volatile (at room temperature) polyol in amounts of about 1 to about 20% (by weight), preferably about 3% to about 8% (by weight). Suitable

polyols include polyethylene glycol, polypropylene glycol and copolymers of ethylene oxide and propylene oxide and glycerol. The copolymers of ethylene oxide and propyiene oxide should be of the general formula HO(-CH₃CHCH₂O-)_m-(CH₂CH₂O)_n-CH₂CH₂OH where m and n are positive integers. The invention is generally directed to a coating for an intracorporeal device and particularly to an expandable portion of intraluminal catheter such as the balloon on a dilatation catheter for coronary angioplasty. The dilatation catheters have an elongated catheter shaft with at least one inner lumen which is adapted to direct inflation liquid therethrough and an inflatable member or balloon on the distal extremity of the catheter shaft which has an interior in fluid communication with the inner lumen within the shaft. The inflatable member or balloon is adapted to dilate body lumens such as stenotic coronary and peripheral arteries, prostatic urethras and the like.

In a presently preferred embodiment, the balloon material is a thermoplastic polymer or a blend of thermoplastic polymers such as polyethylene, polyethylene terephthalate, polyesters (e.g. Nylon) and suitable ionomers.

The balloon of the invention is made by forming a tubular product of the desired polymeric material using conventional melt processing techniques, such as extruding. After the tubular product of the desired composition is formed, it may be blown in a conventional fashion into a relatively inelastic balloon.

The polymers from which the balloon is made may be cross- linked by the use of a suitable cross-linking agent such as a peroxide or an amine, or by irradiation with gamma or electron beam radiation. It is

preferable to incorporate a cross linking agent in amounts ranging from about 0.1 to about 2 %, preferably about 0.1 to about 1 % into the polymer from which the balloon is made before it is formed to facilitate cross-linking upon irradiation. Suitable cross-linking agents include components having carbon-carbon unsaturation, e.g. ethylenic double bonds, such as allyl, methallyl, propargyl or vinyl groups. Preferred cross linking agents include triallyl cyanurate, triallyl isocyanurate, triallyl trimellitate, triallyl trimesate, tetraallyl pyromellitate and the diallyl ester of 1 ,1 ,3-trimethyl-5-carboxy-3-(p-carboxyphenyl) indane.

In one presently preferred method of forming the coating of the invention on the surface of the balloon on a dilatation catheter, the catheter is dipped into an aqueous solution containing about 0.5 to about 20% (by wt.), preferably about 2 to about 7%, polymer solids, which includes the reacted copolymer of the hydrophilic monomeric material and the plasticizing monomeric material and an additional hydrophilic polymer. The catheter is dipped at a rate of about 5 to about 40 cm per minute. Upon removal from the aqueous solution, the catheter is irradiated to cross link the polymeric coating material, e.g. ultraviolet radiation from a mercury lamp for about 10 seconds to about 10 minutes at an intensity of about 5 to about 260 milliwatts, preferably about 10 to about 50 milliwatts, per cm² of catheter surface.

The coating of the invention on the catheter surface, particularly the coating on the balloon, is quite durable, exhibits good flexibility and is characterized by very low coefficients of friction. As a result, the catheter can be readily advanced through guiding catheters and tortuous coronary anatomy. The coating also eases the passage of the balloon into tight stenoses. These and other advantages of the invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accompanying exemplary drawings.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is an elevational view of an over-the-wire dilatation catheter embodying features of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Fig. 1 illustrates a dilatation catheter 10 which includes an elongated catheter shaft 1 comprising an inner tubular member 12 and an outer tubular member 13, a balloon or inflatable member 14 and an adapter 15. The inner tubular member 12 has an inner lumen 16 which is adapted to receive the guidewire 17 and defines with the outer tubular member 13 an annular lumen 18 which is adapted to direct inflation fluid to the interior of the balloon 14. The arm 19 of the adapter 15 directs inflation fluid from a source not shown into the annular lumen.

In the embodiment shown in the drawings, part of the shaft

1 1 and the balloon 14 are provided with a durable yet flexible hydrophilic coating 20 in accordance with the present invention. In other embodiments the balloon 14 alone may be provided with the flexible hydrophilic coating of the invention.

The dry coating thickness of the hydrophilic coating generally will range from about 0.00002 to about 0.001 inch (0.0005- 0.025 mm), preferably about 0.00005 to about 0.0005 inch (0.0013-

0.013 mm).

The materials of construction of the various catheter components such as the inner tubular member 12 and the adapter 15

may be formed of conventional materials, e.g. polyethylene, polyvinyl chloride, polyamide and the like. The means used to join the various catheter components may be conventional such as by heat or laser bonding, heat shrinking or use of a suitable adhesive. The various catheter components will generally be of conventional size depending upon the intended end use. The following is a example of applying a coating to the distal portion of a balloon dilatation catheter for angioplasty procedures. The catheter surface was first cleaned with 2-propanol and plasma treated with oxygen to prepare the surface for optimal coating adhesion. The catheter was dipped into an aqueous bath containing 3% polymer solids which includes about 50% of a first hydrophilic polymer and about 50% of a second hydrophilic polymer which is a copolymer of a hydrophilic monomer and a plasticizer monomer in accordance with the invention. The bath was maintained at a temperature of about 20 ^* C. The catheter surface was then subjected to ultraviolet radiation from a mercury lamp at an intensity of 12 milliwatts/cm² for about 3 minutes to cure the coating. Two coats were applied in essentially the same manner. The coating was found to be durable, very flexible and lubricous. When subjected to an aqueous based liquid, the coating had a coefficient of friction of about 0.03. No cracks or delaminations of the coating were noted.

The first hydrophilic polymer was a polymer material sold by the Bio-Metric Systems, Inc. (BSD, under the designation PV05 which is a polymer primarily formed of n-vinyl pyrrolidone. The polymer material as

sold had been treated to attach latent photoactive groups to facilitate the bonding of the reacted polymer to the desired substrate, as taught in U.S.

Patent 5,002,582 and the other patent incorporated by reference. The second hydrophilic polymer was a polymer material sold by BSI under the designation PA05 which is a polymer primarily formed of acrylamide, but which included 7.2% methoxy polyethylene glycol (1000 mol. wt.) mono methacrylate (Methoxy PEG 1000 MMA). The second polymer as sold had likewise been treated to attach latent photoactive groups to facilitate the bonding of the reacted polymer to the desired substrate as previously described.

In another example, a 3% polymer solids bath was prepared containing 1.5% PV05 and 1.5% PA03 which is the same as PA05 but without the Methoxy PEG 1000 MMa plasticizing monomer. A coating was prepared on the balloon of a dilatation catheter in the same manner as in the previous example. The dry, cured coating formed cracks and some coating segments delaminated from the underlying balloon surface which potentially can reduce performance and result in in-vivo particle generation.

While the detailed description of the invention has been described herein in terms of a presently preferred embodiment comprising a balloon dilatation catheter for PTCA, those skilled in the art will recognize that the coating of the invention may be employed in a wide variety of devices in contact with various body fluids both intracorporeally and extracorporeally. For example, the coating may be utilized on catheters adapted to dilate prostatic urethras and other body lumens and the coating can be utilized on dialysis machines. Likewise, other

modifications and improvements may be made to the present invention

without departing from the scope of the invention.

Claims

WHAT IS CLAIMED IS: 1. A flexible hydrophilic coating comprising the reaction product

of: a) a hydrophilic monomer; and b) a plasticizer monomer.

2. The hydrophilic coating of claim 1 wherein the reaction product includes at least about 50% of hydrophilic monomer and from about 5 to about 50% of plasticizer monomer.

3. The hydrophilic coating of claim 1 wherein the hydrophilic monomer has the formula R<_jCH ⁼ CR₂π₃ where R1 is a hydrogen or pyrrolidone, R2 is a hydrogen or a methyl group, R3 is a hydrogen or -COR₄, and R₄ is -NH₂, -OH, -NHC(CH₃)₂CH₂COR₆, -N(CH₃)₂, -O(CH₂)_nOH, or -OCH₃CHCH₂OH, where R₅ is CH₃ or OH, and n is 1 or 2

4. The coating of claim 1 wherein the plasticizer monomer is

hydrophilic.

5. The coating of claim 2 wherein the hydrophilic plasticizer monomer has the formula

CH₂ = CR₆-COO(CH₂CH₂O)_nCH₂CH₂OR_β where R_β is a hydrogen or methyl group.

6. The coating of claim 3 wherein the hydrophilic plasticizer

monomer is selected from at least one of the group consisting of methoxy poly(ethylene glycol) monomethacrylate, polyethylene glycol) monomethacrylate, methoxy poly(ethylene glycol) acrylate and poly(ethylene glycol) acrylate.

7. The coating of claim 6 wherein the selected hydrophilic plasticizer monomer has a molecular weight from about 500 to about 1500.

8. The coating of claim 1 wherein the plasticizer monomer is a hydrophobic plasticizer having the general formula CH₂C = COOR₅ where R_s is a straight chain or branched alkyl group having from 2 to 22 carbon atoms.

9. The coating of claim 8 wherein the plasticizer monomer is selected from at least one of the group consisting of 2-ethyl hexl acrylate, n-butyi acrylate and stearyl methacrylate.

10. The flexible hydrophilic coating of claim 1 wherein the hydrophilic monmeric material is partially polymerized with the plasticizer monomer and then a water soluble, relatively non-volatile polyol in an amount of about 1 to about 20% is incorporated into the partially polymerized monomeric material.

1 1. The flexible hydrophilic coating of claim 1 wherein the hydrophilic monmeric material is partially polymerize with the plasticizer monomer and then a water soluble, relatively non-volatile polyol in amounts of about 3 to about 8% are incorporated into the partially

polymerized monomeric material.

12. The flexible hydrophilic coating of claim 10 wherein the polyol is selected from one or more of the group consisting of polyethylene glycol, polypropylene glycol and copolymers of ethylene oxide and propylene oxide and glycerol.

13. The hydrophilic coating of claim 12 wherein the copolymers

of ethylene oxide and propylene oxide have the general formula HO(-CH₃CHCH₂O-)_m-(CH₂CH₂O)_n-CH₂CH₂OH

where m and n are positive integers.

14. The hydrophilic coating of claim 1 wherein the copolymer comprises at least 30% of the components thereof.

15. The hydrophilic coating of claim 1 wherein the copolymer comprises at least 40% of the components thereof.

16. The hydrophilic coating of claim 15 including up to 50% of one or more additional hydrophilic polymers.

17. An intraluminal catheter having a flexible hydrophilic coating at least on an exterior portion thereof which comprises: a) at least about 50% by weight of a hydrophilic monomer having the formula

R,CH = CR₂R₃

where R1 is a hydrogen or pyrrolidone, R2 is a hydrogen or a methyl group, R3 is a hydrogen or -COR₄, and R₄ is -NH₂, -OH, -NHC(CH₃)₂CH₂COR₅, -N(CH₃)₂, -O(CH₂)_nOH, or -OCH₃CHCH₂OH, where R₆ is CH₃ or OH, and n is 1 or 2; and b) from about 5 to about 50% of a plasticizer monomer.

18. The intraluminal catheter of claim 17 wherein the plasticizer

is a hydrophilic plasticizer.

19. The intraluminal catheter of claim 18 wherein the hydrophilic plasticizer is CH₂ = CR₆-COO(CH₂CH₂O)_nCH₂CH₂OH where R₆ is a hydrogen or methyl group.

20. The intraluminal catheter of claim 17 wherein the hydrophilic plasticizer is selected from one or more of the group consisting of methoxy poly(ethylene glycol) monomethacrylate, poly(ethylene glycol) monomethacrylate, methoxy poly(ethylene glycol) acrylate and poly(ethylene glycol) acrylate.

21. The intraluminal catheter of claim 20 wherein the selected hydrophilic plasticizer has a molecular weight from about 500 to about 1500.

22. The intraluminal catheter of claim 17 wherein the plasticizer material is at least in part a hydrophobic plasticizer having the general formula CH₂C = COOR₅ where R₅ is a straight chain or branched alkyl group having from 2 to 22 carbon atoms.

23. The intraluminal catheter of claim 22 wherein the hydrophobic plasticizer is selected from at least one of the group consisting of 2-ethyl hexl acrylate, n-butyl acrylate and stearyl methacrylate.

24. In a balloon dilatation catheter having an elongated shaft and an inflatable dilatation member on a distal portion of the elongated shaft, the improvement comprising a hydrophilic coating on at least the exterior of the balloon which comprises the reaction product of:

a) at least about 50% by weight of a hydrophilic monomer having the formula R₁CH = CR₂R₃

where R1 is a hydrogen or pyrrolidone, R2 is a hydrogen or a methyl group, R3 is a hydrogen or -COR₄, and R₄ is -NH₂, -OH, -NHC(CH₃)₂CH₂COR₆, -N(CH₃)₂, -O(CH₂)_nOH, or -OCH₃CHCH₂OH, where R₅ is CH₃ or OH, and n is 1 or 2; and b) from about 5 to about 50% of a hydrophilic plasticizer monomer having the formula CH₂ = CR₆-COO(CH₂CH₂O)_nCH₂CH₂OH where R₆ is a hydrogen or methyl group.

25. The dilatation catheter of claim 24 wherein the hydrophilic plasticizer is selected from one or more of the group consisting of methoxy poly(ethylene glycol) monomethacrylate, poly(ethylene glycol) monomethacrylate, methoxy poly(ethyiene glycol) acrylate and poiy(ethylene glycol) acrylate.

26. The dilatation catheter of claim 25 wherein the selected hydrophilic plasticizer has a molecular weight from about 500 to about 1500.

27. The dilatation catheter of claim 24 wherein the copolymer comprises at least 30% of the coating.

28. The dilatation catheter of claim 24 wherein the copolymer comprises at least 40% of the coating.

29. The dilatation catheter of claim 28 wherein the coating includes up to 50% at least one additional hydrophilic polymers.

30. The dilatation catheter of claim 24 wherein the copolymer is bonded to the balloon by means of latent photoactive groups.

31. The dilatation catheter of claim 29 wherein the additional

hydrophilic polymer is n-vinyl pyrrolidone.