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Publication numberCA2144633 A1
Publication typeApplication
Application numberCA 2144633
PCT numberPCT/US1994/008515
Publication date16 Feb 1995
Filing date27 Jul 1994
Priority date27 Jul 1993
Also published asEP0706318A1, EP0706318A4, US5443455, US5750206, WO1995004839A2, WO1995004839A3
Publication numberCA 2144633, CA 2144633 A1, CA 2144633A1, CA-A1-2144633, CA2144633 A1, CA2144633A1, PCT/1994/8515, PCT/US/1994/008515, PCT/US/1994/08515, PCT/US/94/008515, PCT/US/94/08515, PCT/US1994/008515, PCT/US1994/08515, PCT/US1994008515, PCT/US199408515, PCT/US94/008515, PCT/US94/08515, PCT/US94008515, PCT/US9408515
InventorsRobert Hergenrother, Uriel Hiram Chee, Laurent Schaller
ApplicantRobert Hergenrother, Uriel Hiram Chee, Laurent Schaller, Target Therapeutics, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: CIPO, Espacenet
Method of pretreating metals for polymer coating
CA 2144633 A1
Abstract
This invention relates to a new technique for preparing metal devices such as guide wires for the subsequent attachment of hydrophilic coatings. The invention also relates to guide wires (10), and other devices made according to that method. In one embodiment of the method of this invention, a hydrocarbon residue undercoat (14) is applied to a metal guide wire core (12) by plasma deposition. A photoactive hydrophilic polymer (16) is then deposited on the hydrocarbon residue coating (14) and activated by ultraviolet light. The hydrocarbon residue coating (14) acts as a tie layer between the hydrophilic polymer (16) and the metal guide wire core (12) apparently by providing C-C bonds for the covalent linking of the coating material to the tie layer (14). The resulting article of this invention is a guide wire (10) having the maneuverability of a metal guide wire and the biocompatibility of a lubricious hydrophilic polymer.
Claims(26)
1. A method of pretreating a metal surface for subsequent covalent bonding with a polymer coating comprising the following steps:
placing the metal surface in a plasma chamber;
and exposing the surface to a hydrocarbon plasma within the plasma chamber so to depositing a hydrocarbon residue on the metal surface.
2. The method of claim 1 wherein the metal surface is stainless steel.
3. The method of claim 1 wherein the metal surface is nitinol.
4. The method of claim 1 wherein the hydrocarbon plasma comprises one or more low molecular weight alkanes or alkenes or fluorocarbons.
5. The method of claim 1 further comprising the step of exposing the metal surface to a plasma etch before the step of exposing the surface to the hydrocarbon plasma.
6. The method of claim 5 wherein the plasma etch step comprises exposing the metal surface to oxygen plasma.
7. The method of claim 1 wherein the metal surface comprises a medical device and the polymer coating to be subsequently covalently bonded is a hydrophilic polymer.
8. The method of claim 7 wherein the hydrophilic polymer is selected from the group of polyvinylpyrrolidone and polyacrylamide.
9. A method of coating a metal surface with a polymer comprising the following steps:
exposing the metal surface to a hydrocarbon plasma to deposit a hydrocarbon residue on the metal surface, depositing a photocrosslinkable system on the hydrocarbon residue, the photocrosslinkable system comprising molecules of the polymer and a chemical linking moiety possessing a photochemically reactive group capable upon activation of covalently bonding to the hydrocarbon residue; and activating the photochemically reactive group of the chemical linking moiety to cause the photochemically reactive group to covalently bind to the hydrocarbon residue.
10. The method of claim 9 in which the plasma hydrocarbon comprises at least one member selected from low molecular weight alkanes, alkenes, and fluorocarbons.
11. The method of claim 10 in which the plasma hydrocarbon is methane.
12. The method of claim 9 in which the polymer is a hydrophilic polymer.
13. The method of claim 12 in which the hydrophilic polymer comprises polyvinylpyrrolidone.
14. The method of claim 13 in which the hydrophilic polymer further comprises polyacrylamide.
15. A method of coating a metal surface with a polymer comprising the following steps:
depositing a hydrocarbon residue on the metal surface by exposing the metal surface to a hydrocarbon plasma; and covalently bonding the polymer to the hydrocarbon residue.
16. The method of claim 15 in which the hydrocarbon plasma comprises at least one member selected from low molecular weight alkanes, alkenes, and fluorocarbons.
17. The method of claim 16 in which the hydrocarbon plasma is methane.
18. The method of claim 16 in which the polymer is a hydrophilic polymer.
19. The method of claim 18 in which the hydrophilic polymer comprises polyvinylpyrrolidone.
20. The method of claim 19 in which the hydrophilic polymer further comprises polyacrylamide.
21. A guidewire comprising a metal core, a plasma deposited hydrocarbon residue tie layer surrounding at least a portion of the metal core, and an outer polymer coating covalently bonded to the tie layer.
22. The guidewire of claim 21 in which the metal core comprises stainless steel.
23. The guidewire of claim 21 in which the metal core comprises nitinol.
24. The guidewire of claim 21 in which the outer polymer coating comprises a hydrophilic polymer.
25. The guidewire of claim 24 in which the hydrophilic polymer comprises polyvinylpyrrolidone.
26. The guidewire of claim 24 in which the hydrophilic polymer comprises polyacrylamide.
Description  (OCR text may contain errors)

21~4G~
W095/~U~9 PCT~S94/08515 .

., METHOD OF PRETREATING METALS FOR POLYMER COATING

Field of the Invention This invention relates generally to a method for preparing a surface for subsequent attachment of a coating and, in particular, to a method for preparing a metal surface for subRequent covalent linking to a polymer coating. This invention also relates to articles such as medical devices made according to this method.

Background of the Invention The surface of an object may be coated with a polymer to protect the surface or to provide the surface with properties of the polymer coating. For example, coatings of synthetic polymers and natural biomolecules are applied to medical devices for a variety of reasons.
In the case of catheters and guidewires, it is desirable to add a coating with a low coefficient of friction in the presence of water and a low tendency to form clots (thromboembolisms) in the presence of blood.
As discuRsed in U.S. Patent No. 5,002,582, the disclosure of which is incorporated herein by reference, polymer molecule~ may be provided with latent reactive groups covalently bonded to them such that when the molecules are brought into bonding proximity with a surface (such as on a medical device), the latent reactive groups can be energized to form, via free active species generation, covalent bonds between these molecules and the surface. The latent reactive groups generate active species such as free radicals, nitrenes, 214~
W095/0~9 2 PCT~S94/0851 carbenes, and excited states of ketones upon absorption of external electromagnetic or kinetic (thermal) energy.
The '582 patent describes a number of suitable latent reactive groups and some methods of applying polymers and other coatings to a surface using the latent reactive groups. Under one method, a solution cont~;n;ng a latent reactive molecule (e.g., a molecule having a latent reactive group) is applied to the surface.
Thereafter, the desired polymer is brought into contact with, and is covalently bonded to, the latent reactive molecule, as to a reactive group different from the latent reactive group, to form a photocrosslinkable polymer system. The latent reactive groups may then be activated to cause the photocrosslinkable polymer system to covalently bond to the surface.
Under another method disclosed in the '582 patent, the surface is first coated with a solution of the molecules bearing latent reactive groups. W light i8 applied to cause the molecules to covalently bond, through the latent reactive groups, to the surface. A
solution cont~;n;ng the desired polymer is then applied to the surface, and the polymer bonds covalently to the photoactively treated surface. Further details of photoactive and thermally active covalent attachment of polymers may be found in U.S. Patents Nos. 4,722,906;
4,973,493; and 4,979,959. The disclosures of these patents are incorporated herein by reference.
Bio-Metric Systems, Inc., markets a photoactive biocompatible coating technique under the trademark BioCoat. This technique first combines a photoactive binder and the desired coating material, such as a hydrophilic polymer, to create a photocrosslinkable polymer system. A solution of the photocro~slinkable polymer system is then applied to the medical device.
The coating is dried, and the binder is cured with W

3 ~
W095/04839 PCT~S94/08515 light to covalently bond the hydrophilic photocrosslinkable polymer system to the surface of the device.
Catheter guidewires are one example of the kind of medical device typically coated with a biocompatible material. In order to facilitate insertion of the guidewire into a patient and to m;n;m;ze the threat of thromboembolisms, the metal core must be surrounded by a lubricious hydrophilic polymer coating. The coatings of prior art guidewires, however, are inadequate, for the reasons stated below.
The BioCoat process and the processes disclosed in U.S. Patents Nos. 4,722,906; 4,973,493; 4,979,959; and 5,002,582 have not been used successfully to coat metal devices such as guidewires with hydrophilic polymers (despite suggestions to the contrary in those references) without first preparing or pretreating the surface of the devices, particularly when the coated metal devices are used in an aqueous environment. Two possible pretreatments have been proposed. Under one approach, the guidewire is prepared for subsequent coating by shrink-wrapping a polyethylene sleeve around the guidewire. The photocrosslinkable hydrophilic polymer ~ystem is then applied, dried and cured as described above. In another possible pretreatment method, the guidewire is prepared for subsequent coating by dipping the guidewire in a silane undercoat solution, then drying. The photocrosslinkable hydrophilic polymer system is then applied to the silane undercoating.
Other prior art methods of applying biocompatible coatings to metal devices use preparation methods that fall into the same two categories as the photoactive binder approaches mentioned above: (1) wet undercoat pretreatment methods and (2) solid sleeve undercoat pretreatment methods. For example, a wet WO9g~Y PCT~S94/08S15 undercoat method of applying a biocompatible, hydrophilic coating to a catheter or guidewire i8 disclosed in U.S.
Patent No. 5,135,516. The coating described in the '516 patent comprises an isocyanate primer, a lubricious binding component and an antithrombogenic component. The binding component is a hydrophilic, water-swellable, acid-cont~;n;ng polymer with quaternary ~mmon;um cations bonded into the polymer layer. In one disclosed application method, a stainless steel guidewire is coated first with a primer solution of a 1~ polyisocyanate in methylethylketone, then dried for 30 minutes. A topcoat of 1~ poly(acrylic acid) and 0.5~ of MYRJ 53 (nonionic surfactant) in dimethylformamide is then applied and dried for another 30 minutes. The resulting hydrophilic surface is then dipped first in a b~n~lkonium chloride solution, then dried and dipped in a heparin salt solution to complete the process.
U.S. Patent No. 5,129,890 describes a solid sleeve pretreatment method for coating a metal guidewire with a lubricious coating. The guidewire coating method disclosed in the '890 patent interposes a polyurethane sleeve between the hydrophilic coating and the guidewire.
The sleeve provides an attachment base for the hydrophilic coating.
Summary of the Invention One drawback of prior art wet undercoat preparation methods of coating metal devices with biocompatible hydrophilic polymers is the time needed to apply and dry the undercoat before the application of the hydrophilic polymer itself. Another drawback of prior wet undercoat pretreatment methods is the difficulty of obt~;n;ng an even layer of the wet undercoat. Any irregularities in the thickness of the undercoat will affect the quality of the hydrophilic outer coating.

~1 ~4633 ~ W095/0~9 PCT~S94/08515 The use of wet treatment methods is additionally becoming increasingly more of an environmental concern. The materials used in cleaning, coating, and rinsing the medical devices are now often difficult, or at least very expensive, to dispose of.
Another drawback of wet undercoating techniques is the drying time required for each coating layer.
~onger manufacturing times translate into higher manufacturing co~ts and can make the resulting article prohibitively expensive.
A drawback of the solid sleeve undercoat approach is the thickness of the resulting product. The combined thicknesses of the sleeve and hydrophilic coating makes the guidewire less maneuverable and harder to use. If, on the other hand, the guidewire diameter is made th; nner in order to accommodate the additional thickness of the sleeve, the guidewire will be less stiff and harder to control. What is needed, therefore, is a method for preparing metal devices such as guidewires for subsequent application of hydrophilic coatings that avoids these and other problems.
This invention relates to a new technique for preparing metal devices such as guidewires for the subsequent attachment of hydrophilic coatings. The invention also relates to guidewires and other devices made according to that method.
In one embodiment of the method of this invention, a hydrocarbon residue undercoat is applied to a metal guidewire core by plasma deposition. A
photoactive hydrophilic polymer is then deposited on the hydrocarbon residue coating and activated by ultraviolet light. The hydrocarbon residue coating acts as a tie-layer between the hydrophilic polymer and the metal guidewire core by providing C-C bonds for the covalent linking of the coating material to the tie-layer. The 2~ ~4~33 wogs/nU~9 PCT~S94/0851~

resulting article of this invention is a guidewire having the maneuverability of a completely metal guidewire and the biocompatibility of a lubricious, hydrophilic polymer.
The invention i8 described in more detail below with reference to the drawings.

Brief Description of the Drawin~s Figure 1 is a plan view of a guidewire made according to the method of this invention.
Figure 2 is a cross-sectional drawing of a portion of the guidewire of Figure 1.

Description of the Invention This invention is a method for preparing or pretreating guidewires and other metal devices to receive a subsequent coating of a polymer, preferably a polymer which is lubricious, biocompatible, and hydrophilic. The preferred method will be discussed in relation to a metal guidewire. A metal guidewire core is placed in a plasma chamber and cleaned with an oxygen plasma etch. The guidewire core is then exposed to a hydrocarbon plasma to deposit a plasma-polymerized tie layer on the guidewire core to complete the pretreatment. The hydrocarbon plasma may comprise a lower molecular weight (or gaseous) alkanes such as methane, ethane, propane, isobutane, butane or the like; lower molecular weight alkenes such as ethene, propene, isobutene, butene or the like or;
gaseous fluorocarbons such as tetrafluoromethane, trichlorofluoromethane, dichlorodifluoromethane, trifluorochloromethane, tetrafluoroethylene, trichlorofluoroethylene, dichlorodifluoroethylene, trifluorochloroethylene and other such material~.
Mixtures of these materials are also acceptable. The tie layer apparently provides C-C bonds for subsequent W095/0~9 ~14 ~ 6 3 3 PCT~S94/08515 covalent bonding to the outer hydrophilic polymer coating. Preferred flow rates for the hydrocarbon into the plasma chamber are in the range of 500 c.c./min. to 2000 c.c./min. and the residence time of the guidewire in the chamber is in the range of 1-20 minutes, depending on the chosen hydrocarbon and the plasma chamber operating parameters. Power settings for the plasma chamber are preferably in the range of 200W to 1500W.
The pretreated guidewire may be coated by a polymer in a manner known in the prior art. For example, in one embodiment of the preferred apparatus of this invention, the pretreated guidewire is dipped in a solution of a photoactive hydrophilic polymer system, i.e., a latently photoreactive binder group covalently bonded to a hydrophilic polymer. After drying, the coated guidewire is cured by exposing it to W light.
The W light activates the latently reactive group in the photoactive polymer system to form covalent bonds with crosslinked C-C bonds in the hydrocarbon residue tie layer. The dipping and curing steps are preferably repeated often enough, typically twice, to achieve the appropriate thickness of the hydrophilic coating layer.
One preferred e-mbodiment of a product made according to this invention is shown in Figures 1 and 2.
A metal guidewire 10 is coated over most of its length by a lubricious hydrophilic polymer. The guidewire has an uncoated region 20 at its pro~;m~l end to provide the user with a gripping surface.
Figure 2 schematically depicts a cross-section of the guidewire of Figure 1. The d;m~n~ions have been exaggerated to better show the individual elements of the invention. Guidewire 10 has a metal core 12, preferably 0.010 to 0.025" thick stainless steel or nitinol. The exterior surface of guidewire 10 is a biocompatible coating 16 of a polyacrylamide/polyvinylpyrrolidone 2144 63~
W095/0~9 8 PCT~S94/0851 mixture bonded to a photoactive binding agent. The lubricious and hydrophilic character of coating 16 facilitates insertion of the guidewire into a patient and helps reduce the incidence of thromboemboli while the guidewire is within the patient's body. In the preferred embodiment, coating 16 is made from a mixture of Bio-Metric Systems PA03 and PV01 binding systems according to Examples 1-4 below.
A tie layer 14 of plasma produced hydrocarbon residue having a thickness on the order of loA thick is diRposed between core 12 and coating 16. This process typically produces layers of hydrocarbon residue less than about lo00A in thickness, and more typically less than about looA. Tie layer 14 effectively bonds layer 16 to metal core 12 while adding very little additional bulk to the guidewire. Guidewires made according to this invention therefore avoid the size and maneuverability problems of prior art guidewires.
Other materials may be substituted for the materials of the preferred embodiment without departing from the invention. For example, the guidewire core may be made from stainless steel, nitinol, or platinum with a diameter in the range of 0.010"-0.038".
The photoactive hydrophilic polymer system of this preferred embodiment is a mixture of Bio-Metric Systems PA03 polyacrylamide/binder system and Bio-Metric Systems PA01 polyvinylpyrrolidone system. The polyacrylamide system provides lubricity, and the polyvinylpyrrolidone system provides both lubricity and binding for durability. The exact proportions of the two systems may be varied to suit the application. As an alternative, however, the hydrophilic biocompatible coating may be polyacrylamide alone, polyvinylpyrrolidone alone, polyethylene oxide, or any suitable coating known in the art. In addition, a coating of heparin, albumin 21~63~
WOg5/04839 PCT~S94/08515 or other proteins may deposited over the hydrophilic coating in a manner known in the art to provide additional biocompatibility ~eatures.
The guidewire or other device may be cleaned by using an argon plasma etch in place of the oxygen plasma etch. The thickness of the plasma-polymerized tie layer may also vary without departing from the scope of this invention.
The following examples are further illustrative of the articles and methods of this invention. The invention is not limited to these examples.

Exam~le 1 A 0.014" diameter stainless tapered steel guidewire was placed in a Plasma Etch MK II plasma chamber and cleaned with an oxygen plasma for 2 minutes.
Ethane flowing at a rate of 700 c.c./min. was admitted 20 into the chamber, and the chamber was operated at a power setting of 800W for 5 minutes to plasma treat the ethane into a hydrocarbon residue on the surface of the wire.
All but approximately six inches of the wire was dipped in a polyvinylpyrrolidone/polyacrylamide (PVP/PA) 25 photocrosslinkable solution consisting essentially a mixture of 50~ BSI PV01 and 50~ BSI PA03. The coated guidewire was then dried and exposed to an ultraviolet light (325 nm.) for 8 seconds. The dipping, drying and exposing steps were repeated twice. When wetted, the 30 resulting wire felt lubricious and required less force to pull through an 0.018" ID catheter than an uncoated wire.

Example 2 A 0.014" diameter stainless tapered steel 35 guidewire was placed in a Plasma Etch MK II plasma 21~633 W095/0~9 1 0 PCT~S94/08515 chamber and cleaned with an oxygen plasma for 2 minutes.
Ethane flowing at a rate of 1200 c.c./min. was admitted into the chamber, and the chamber operated at a power setting of lOOOW for 5 minutes to plasma treat the ethane into a hydrocarbonaceous rseidue on the su***rface of the wire. All but approximately six inches of the wire was dipped in a polyvinylpyrrolidone/polyacrylamide tPVP/PA) photocrosslinkable solution of a mixture of 33~ BSI PV01 and 67~ BSI PA03. The coated guidewire was then dried and exposed to an ultra~iolet light (325 nm.) for 8 seconds. The dipping, drying, and exposing steps were repeated. When wetted, the resulting wire felt lubricious and required less force to pull through an 0.018" ID catheter than an uncoated wire.
Example 3 A 0.016" diameter nitinol guidewire was placed in a Plasma Etch MK II plasma chamber and cleaned with an oxygen plasma for 10 minutes. Methane flowing at a rate of 2000 c.c./min. was admitted into the chamber, and the chamber operated at a power setting of 400W for 2 minutes to deposit a hydrocarbonaceous residue onto the surface of the wire. All but approximately six inches of the wire was dipped in a polyvinylpyrrolidone/polyacrylamide (PVP/PA) photocrosslinkable solution of a mixture of 67~
BSI PV01 and 33~ BSI PA03. The coated guidewire was then dried and exposed to an ultraviolet light (325 nm.) for 8 seconds. The dipping, drying, and exposing steps were repeated twice. When wetted, the resulting wire felt lubricious and required less force to pull through an 0.018" ID catheter than an uncoated wire.

Rx~le 4 A 0.016 n diameter nitinol guidewire was placed in a Plasma Etch MK II plasma chamber and cleaned with an ~ WOs5/0~9 21~ 4 6 3 3 PCT~S94/08515 oxygen plasma for 10 minutes. Methane flowing at a rate of 1500 c.c./min. was admitted into the chamber, and the chamber was operated at a power setting of 600W for 5 minutes to plasma treat the methane into a 5 hydrocarbonaceous on the surface of the wire. All but J approximately 8iX inches of the wire was dipped in a polyvinylpyrrolidone/polyacrylamide (PVP/PA) photocrosslinkable solution consisting essentially a mixture of 50~ BSI PV01 and 50~ BSI PA03. The coated 10 guidewire was then dried and exposed to an ultraviolet light (325 nm.) for 8 seconds. The dipping, drying, and exposing steps were repeated. When wetted, the resulting wire felt lubricious and required less force to pull through an 0.018" ID catheter than an uncoated wire.
~ample 5 A 0.016" diameter nitinol guidewire was placed in a Plasma Etch MK II plasma chamber and cleaned with an oxygen plasma for 10 minutes. Ethane flowing at a rate 20 of 900 c.c./min. was admitted into the chamber, and the chamber was operated at a power setting of 600W for 10 minutes to deposit a hydrocarbon residue onto the surface of the wire. All but approximately six inches of the wire was dipped in a polyvinylpyrrolidone/polyacrylamide 25 (PVP/PA) photocrosslinkable solution of a mixture of 33~
BSI PV01 and 67~ BSI PA03. The coated guidewire was then dried and exposed to an ultraviolet light (325 nm.) for 8 seconds. The dipping, drying, and exposing steps were repeated twice. When wetted, the resulting wire felt 30 lubricious and required less force to pull through an 0.018" ID catheter than an uncoated wire.

~ample 6 An 0.014" diameter stainless steel wire was 35 placed in an Advanced Plasma Systems plasma chamber and 2~4~33 W095/OU~9 1 2 PCT~S94/0851s cleaned with an oxygen plasma. Tetrafluoroethylene flowing at a rate of 1000 c.c./min. was admitted into the chamber, and the chamber was operated at a power setting of lOOOW for 10 minutes.to deposit a fluorocarbon residue onto the surface of the wire. All but approximately six inches of the wire was dipped in a polyvinyl-pyrrolidone/polyacrylamide (PVP/PA) photocrosslinkable solution of a mixture of 67~ BSI PV01 and 33~ BSI PA03.
The coated guidewire was then dried and exposed to an ultraviolet light (325 nm.) for 8 seconds. The dipping, drying, and exposing steps were repeated twice. When wetted, the resulting wire felt lubricious and required less force to pull through an 0.018 n ID catheter than an uncoated wire.
Exam~le 7 An 0.016" diameter stainless steel wire was placed in an Advanced Plasma Systems plasma chamber and cleaned with an oxygen plasma. Tetrafluoromethane flowing at a rate of 1500 c.c./min. was admitted into the chamber, and the chamber was operated at a power setting of 1200W for 10 minutes to deposit a fluorocarbon residue onto the surface of the wire. All but approximately six inches of the wire was dipped in a polyvinyl-pyrrolidone/polyacrylamide (PVP/PA) photocrosslinkablesolution of a mixture of 50~ BSI PV01 and 50~ BSI PA03.
The coated guidewire was then dried and exposed to an ultraviolet light (325 nm.) for 8 seconds. The dipping, drying, and exposing steps were repeated twice. When wetted, the resulting wire felt lubricious and required less force to pull through an 0.018 n ID catheter than an uncoated wire.

Classifications
International ClassificationA61L33/00, A61L29/08, C23C16/50, B32B15/08, A61M25/09, C23C16/30
Cooperative ClassificationY10T428/2942, A61L29/085, A61L33/0029, A61M25/09
European ClassificationA61L29/08B, A61L33/00H2F, A61M25/09
Legal Events
DateCodeEventDescription
14 Mar 1995EEERExamination request
27 Jul 1998FZDEDead