CA2019636A1

CA2019636A1 - Medical apparatus having protective lubricious coating

Info

Publication number: CA2019636A1
Application number: CA002019636A
Authority: CA
Inventors: Margaret Palmer Kiezulas
Original assignee: Margaret Palmer Kiezulas; C.R. Bard, Inc.
Current assignee: CR Bard Inc
Priority date: 1989-06-23
Filing date: 1990-06-22
Publication date: 1990-12-23
Also published as: CN1048875A; JPH0351052A; NZ234127A; US5026607A; AU5713590A; KR910000195A

Abstract

0129h MEDICAL APPARATUS HAVING PROTECTIVE, LUBRICIOUS COATING

Abstract of the Disclosure - A method for providing a medical apparatus with a protective, lubricious coating is described. The method comprises providing a coating solution which contains a protective compound such as a urethane, a slip additive such as a siloxane, and optionally, a crosslinking agent for the protective compound such as a polyfunctional aziridine, coating the solution onto a surface of a medical apparatus and allowing the coating to set. m e resulting surface coating is lubricious, tough and flexible. The coating is well suited for use with materials used as components of balloon catheters.

Description

2 ~ 3 ~ ~

0129h MEDICAL APPARATUS HAVIN~ PROTECTIVE, LUBRICIOUS COATING

Backqround of the Invention In coronary angioplasty and related technologies, a cstheter having an inflatable balloon attachet at the catheter's distal end i~
employed. 8uch balloon~ have been known to fail by damage resulting from abrasion and puncture durin~
handling and use and also from over-inflation.
lo Additionally, the balloons and catheters upan which they are mounted qenerally have a higher coefficient of friction than desired for ease of use. Thu8, it often becomes difficult to guide the catheter into a desired location in a patient due to friction 15 between the apparatus and the vessel through which the apparatus passes.
A variety of urethane based coating com~ositions for medical applications are known in the art. For example, U.S. Patent 4,642,267 to Creasy et al.
20 describes hydrophilic polymer blends useful for ~-coating catheters and other surfaces. The coating ' '' ' : ............. :' ' :, .

" 2~ 3~ f . .

0129h _ - 2 -comprises a thermoplastic polyurethane and a hydrophilic poly (N-vinyl lactam) such as polyvinylpyrrolidone. Additional components such as crosslinking agents and wax dispersions can be added to the blend. U.S. Patent 4,675,361 to Ward, Jr.
relates to polymer systems useful for coating surfaces having blood and tissue contacting applications. The sys~em comprises a base polymer, such as a polyuretha~e, containing at least one polymer add.tive comprising a segmented block copolymer having both hard and soft segments.
Although each of these patants descri~es an applicat~on involving biomedical apparatus, a need st~ll exist~ for a simple, easy-to-apply coating which i8 biocompatible, lubricious and provides a protective layer to the surface upon which it ig ~- --appl~ed. - .

Summary of the Invention In a broad sense, the present invention comprises medical apparatus having a coating which comprises a protective compound and a slip additive. The protective compound serves to protect t~e surface upon which it i8 coated and to provide a network to contain the slip additive. Urethanes arQ
particularly desirable as the protective compound 2 ~

Bo410/7096 0129h due to their protective qualities and water-based urethanes are especially preferred due to their ability to provide a carboxyl functionality to the coating. Carboxyl functionality allows crosslinking of the coating with carboxyl groups present on the surface of the apparatus to bind the coating to the surface and also allows crosslinking within the urethane itself to provide added strength and toughness to the coating.
The coating is formed on a surface by a method which comprise~ providing a coating solution having between about 2% and about 80% solids, preferably between about 15% and about 25% solids, and which contain~ the protective compound, the slip additive, and optionally, a crosslinking agent for the protective compound; the solutio~ i8 applied to a - surace-using any of a variety of methods for surface coating, and the coating is allowed to set into a protective, lubricious layer upon the apparatus surface.
In a preferred embodiment, the protective compound is a urethane, the slip additive is a dimethyl siloxane, and the crosslinking agent for the urethane is a polyfunctional aziridine.
The coating and method is particularly well suited for use on materials such as polyetheylene terephthalate (PET), a polymeric material having -2 ~

0129h many properties which render it desirable for use as an angioplasty balloon.

Detailed DescriPtion of the Invention As used herein, the term "medical apparatus"
means apparatus suited for use in medical applications, particularly in ~n vivo applications.
8uch apparatus specifically includes, but is not limlted to, balloons, catheters, guidewires, stylets and introducers. Of particular note for use with ~e invent~on are catheters having inflatable balloons such as those developed for use in angioplasty and valvuloplasty, guide catheters and guidewires.
As used herein the term "slip additive" means a chemical compound capabl~ of being included in a protective network to impart a lower coefficient of friction to the network surface. Such compounds include but are not limited to silicon-based compound~ such as silicones and siloxanes, 20 fluorochemicals such as polytetrafluoroethylene (PTFE), and a variety of waxes.
In a prefarred embodiment, the coating is provided in th~ form of a solu~on having a solids co~tent of between about 15% and about 25% and which 25 comprises ~ water-based urethane dispersion, a 2 ~ f' 0129h _ 5 _ dimethyl siloxane emulsion containing at least about 15% solids and a polyfunctional aziridine. Unless otherwise noted, all percentages described herein are percentages by weight. Other materials, such as pigments and radio-opaque compounds can be added as well.
: A high molecular weight, hard, non-yellowing, water-based urethane is preferred as the resin of the coating. Particularly preferred is a urethane dispersion having a solids content of between about 30% and about S0% in a solution comprising a mixture of water, N-Methyl-2-pyrrolidone ~CAS# 872-50-4) and triethyl2minQ (CAS# 121-44-8). Such a dispersion is available from Permuthane (~eabody, MA) as UE41-222. It is particularly desirable that the protective compound be dispersed in a liquid which will not harm the surface upon which the coating is applied. Thus, for a surface such as a PET balloon, the urethane is preferably provided as a dispersion i~ an aqueous medium.
The slip additive is preferably an emulsion of an industrial grade dimethyl siloxane in water having a siloxane content of at least about 15~.
While a slip additive having up to abou~ 100%
25 siloxane or silicone can be used, an aqueous emulsion of the material diluted to about 15% solids i8 easier to handle during mixing of the coating , .

2 ~ 3 ~ ' 0129h solution. A preferred dimethyl siloxane is available from Dow Corning Corporation (Midland, MI) as Q2-3238. This is available neat and can be subsequentl~ combined with water to form an emulsion haYing approximately 15% dimethyl siloxane.
When used in a urethane-based coating, the crossli~iQg agent is preferably a polyfunctional aziridine. Although this material can be diluted prior to use, it is preferably used neat to minimize further dllut~on of the coating solution. Most preferred ~8 the material available from Permuthane (Peabody, MA) as RM10-1703. This material will hydrolyze in water or humid air and reacts rapidly with acid~. Once added to the coating solution, application should be within about ~8 hours if room temperature conditions are maintained. Increased temperature will cause increased hydrolysis, inactivity of the material and promotion of crosslinking of the coating, resulting in a higher coating viscosity. Since the aziridine component is caustic, it must be fully reacted or hydrolyzed before the coated medical apparatus is suitable for _ vivo use.
A most preferred coating formulation has a solids content of approximately 17% u~on application and comprises a mixture containing approximately 42.55% ~E41-222 urethane dispersion, 12.77% Q2-3238 2Q1963~

0129h siloxane dispersion, 2.13% gM10-1703 polyfunctional aziridine and 42.55~ distilled water. The formulation can be made by mixing the siloxane emulsion wit~ the distilled water and subseguen~ly adding the urethane dispersion. This is then mixed in a capped glass container with a magnetic s~irrer until all parts are thoroughly mixed. The crosslinking agent is s~bsequently added to the solution ju~ prior to application of the coating upon a surface. The addition of the crosslinking agent ~ust prior to application of the coating prevents the urethane from crosslinking only with itself and thereby allows a sufficient carboxyl group denæity within the coating for crosslinking 15 with the surface to be coated.
The material can be applied to surfaces using any of a variety of methods.. Preferred among these are dipping, spray coating, rolling and brushing.
Subsequent to the actual coating step, the coated devices are allowed to cure. The curing is preferably carried out by placing the coated devices in ~n o~en at approximately 50C. until the urethane is fully crosslinked.
The resulting coating is flexible, durable and lubricious, retaining its lubricity for an extendéd p~riod of time. These properties are a dir~ct result of the protective compound's ability to act 20~963~

~0410/7096 01~9h . -- 8 --as a binder to maintain domains of the slip additive. Thus the durable binder enhances lubricity by preventing the removal of the slip additive from the substrate surface. Additionally, S the protective compound provides an abrasion resistance to the substrate surface, thereby minimizing the effect of a~use on the device.
In the case of PET balloons, the abrasion resistance provided by the coating is particularly desirable ~ince it substantially reduces damage to the balloon surface. This decreases the likelihood of b~lloon failure caused by mi~handling during balloon preparation or use.
In the case of urethane-based coatings, bonding of th~ coating to the substrate surface upon which it i8 applied can be achieved by a crosslinking reaction between car~oxyl ~unc~ional groups present in the urethane and carboxyl functional groups present on the substrate surface. One method by which such bonding can be achieved involves a crosslinking reaction utilizing the aforementioned polyfunctional aziridine through which the linkage wi 1 1 occu~ .
In a most preferred application, the coating solution is intended to be used to provide a flexible, protective and lubricious coating to the -surface of angioplasty balloons. These balloons can 2019~3~

0129h be made of a variety of materials such as polyvinyl chloride and polyethylene, although polyethylene terephthalate (PET) is preferred. Unfor~unately, PET lacks the reguisite density of available carboxyl groups to provide for satisfactory bonding of the urethane-based coating with the surfaoe.
Therefore, it is often desirable to provide a first layer of a primer material between the PET balloon surface and the coating.
A preferred primer is a dispersion containing an ethylene acrylic acid (EAA) resin. A preferred EAA
resin such as Primacor 5980 available from Dow-Corning Corporation (Midland, MI) can be mixed ln an aqueous solution to provide a formulation containing approximately 25% solids. As with the topcoat formulation, the EAA resin must be applied - from a solvent which will not damage the surface of the apparatus to be coated. When applying the primer to a PET balloon, th~ EAA should be dissolved in an agueous solvent. Since EAA resin has a very low solubility in water, it is necessary to first convert the EAA into a soluble salt. This can be accomplished by combining the resin with a quantity of ammonia sufficient to neutralize the carboxyl groups contained therein. ~-Th2 required amount of ammonia is added to avolume of water into which a sufficient quantity of 2~19~3~

0129h EAA has been mixed to form a dispersion. The container into which the components have been poured i5 then sealed and heated to approximately 110C.
for between about 15 and 30 minutes. The solution is then allowed to cool at which point it is ready for use. It should be noted that during the mixinq steps, it i5 desirable to use a condenser to prevent e~aporation of any of the components prior to sealing the mixing vessel.
As with the topcoat solution, the primer can be applied to the substrate surface using a wide variety of methods including, but not limited to, d~pping, ~pray coat~ng, rolling and brushing. Once applied, the primer should be cured until completely dry. Heat curing at approximately 50C. has been found to be ~atisfactory for the EAA primer - described previously. Subsequen~ly, the topcoat solution can be applied to the primer-coated device surface using the method previously described.
As an alternative to the use of a primer, a surface functionality can be obtained on the substrate surface using a variety of other techniques. For example, surface functionality can be obtained using a plasma or corona discharge or by expo~ing the surface to a flame. In the case of -plasma or corona discharge, the functionality obtained on the surface can be tailored through the 20~63~ f 0129h use of process atmosphere variation. Thus, when an oxygen derived functionality (i.e. -OH or -COOH) is desired, the surface ca~ be plasma treated in an oxygen-containing atmosphere. Alternatively, if an amine functionality is preferred, the treating process can be carried out in a nitrogen-containing atmosphere.
When the surface to be coated comprises a catheter-mounted balloon, it is preferred that the balloon be inflated prior to applying the primer and/or topcoat. This allows the formation of a coating laye~ having a generally uniform thickness and also prQvents adhesion between balloon surfaces that may contact one another in the deflated state.
Care should be taken to ensure that no primer or topcoat i8 allowed to remain within any open lumen - o the catheter as this w~ll likely cause undesirable lumen blockages. Blotting the catheter end and any exposed lumen ports with a suitable 20 blotting material subseguent to applying the layer will prevent such blockages. Alternatively, the catheter lumens can be purged using air or an inert gas.
Since the preferred topcoat solution contains 25 both a slip additive and a crosslinker for the protective compound, th~ solution can be applied to surfaces haYing adequate functional group density in 20~ 9~t36 0129h a single pass. This provides a process efficiency, as it eliminates ~he need to carry out a crosslinking step subsequent to application of the coating to the substrate surface.
When applied to the surface of PET balloons, the coating described herein has resulted in enhanced scratch resistance and a decreased coefficient of friction without noticeably altering the balloon profile or flexibility.
It should be noted that although the preferred coating formulation described herein contains a water-~ased urethane resin and a polyfunctional a~ir~dine crosslinking agent, the invention is not intended to be limited thereto. Rather, the invention is intended to apply to medical apparatus having protective and lubricious coatings provided by a protective resin system containing a slip additive, a~d, optionally, any of a variety of crosslinking agents selected to be compatible with the coating and the surface on which the coating is to be applied. For example, resin systems including but not limited to acrylics, vinylidine chlorides and vinyls can be used as the protective compound and formaldehyde derivatives (melamine, urea, etc.), isocyanates, and carbodiimides are examples of other materials which can be used as crosslinking agents.-In still another embodiment, a urethane resin can be ~019~3~ ~

B0410/70g6 06/23/8g 0129h used in combination with a fluorochemical resin which acts as both a binder and a slip additive.
Preferred fluorochemicals are marketed as FC-10 available from 3M Company and Lumiflon available from ICI Corporation. Such systems can be crosslinked using isocyanates.
ExamPle A coatin~ solution prepared in accordance with the teachings of this invention and having the following formulation was provided:
om~onent SuP~lier/Desiqnation Weiqht %
Urethane Permuthane/UE41-222 42.S5 D~methyl Siloxane Dow/Q2-3238 12.77 Aziridine Permu~hane/KM10-1703 2.13 Water ----- 42.55 The coating solution was applied to a balloon catheter having a 3.0 x 20 mm PET balloon bonded to the catheter with a W -activated adhesive, by dipping the inflated catheter into a volume of the coating mixture. Subsequent to the dipping, the coated apparatus was heat cured at approximately 50C. until dry and then sterilized using ethylene oxide. Testing of the catheter was carried out using an uncoated balloon catheter as a control.
The two ca~heters were individually passed through an 8F tO.072") channel having a curvature r~plicating that of the final curve of an FL4 guide - 201963~

06/23~89 0129h catheter. A 0.14" PTFE-coated guidewire was used.
The force of pushing and pulling the catheter was measured for different insertion lengths and the average minimum and maximum forces (in grams) for 10 cycles of both pushing and pulling of the coated and uncoated catheters were determined. The results of this test are summarized below:
Sample Push - Push Pull Pull (min.) (max.) (min.) ~max.) Coated 11.0 32.S 8.4 25.4 Uncoated 20.5 42.5 16.7 33.0 . . _ ~ Improvement Coated v. Uncoated 46% 21~ 50% 23%
A~ evidenced by the above, the coated catheter 15 displayed a lower resistance to both pushing and pulling through the channei. This reduced resistance represented an average improvement of approximately 34~ overall when comparing the coated catheter to the uncoated control catheter.

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Claims

0129h The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

l. A method for providing a protective, lubricious coating on surfaces of medical apparatus, the method comprising:
a) providing a coating solution having a solids content of between about 2% and about 80% by weight, the coating solution comprising an aqueous dispersion of a urethane having a solids content of between about 30% and about 50%, and a silicone or siloxane emulsion having a solids content of at least about 15%;
b) applying the coating solution to a surface of the medical apparatus; and, c) allowing the coating to set into a layer upon the apparatus surface.
2. A method as in Claim l wherein the coating solution additionally contains a crosslinking agent for the urethane.
3. A method as in Claim 2 wherein the crosslinking agent comprises a polyfunctional aziridine.

0129h
4. A method as in Claim 1 wherein the coating is applied to a polyethylene terephthalate surface.
5. A method as in Claim 4 wherein a primer is applied to the surface prior to applying the coating.
6. A method as in Claim 5 wherein the primer comprises ethylene acrylic acid.
7. A method as in Claim 1 wherein the urethane is dispersed in an aqueous solution containing triethylamine and N-methyl-2-pyrrolidone.
8. A method as in Claim 1 wherein the siloxane is provided as an emulsion of dimethyl siloxane.
9. A method as in Claim 8 wherein the emulsion contains a solids content of about 17%.
10. A method as in Claim 1 wherein the coating solution contains between about 15% and about 25%
solids by weight.
11. A method as in Claim 1 wherein the medical apparatus comprises a balloon.

0129h
12. A method as in Claim 1 wherein the apparatus comprises a catheter.
13. ~ method as in Claim 1 wherein the apparatus comprises a guidewire.
- 14. A medical apparatus having a protective, lubricious surface coating, the coating comprising a crosslinked, water-based urethane compound containing a silicone or siloxane slip additive.
15. An apparatus as in Claim 14 wherein the slip additive comprises dimethyl siloxane.
16. An apparatus as in Claim 14 wherein the surface upon which the coating is applied comprises polyethylene terephthalate.
17. An apparatus as in Claim 16 which comprises a balloon.
18. An apparatus as in Claim 14 which comprises a catheter.
19. An apparatus as in Claim 14 which comprises a guidewire.

0129h
20. An apparatus as in Claim 14 having a primer layer disposed between the coating and the surface
21. An apparatus as in Claim 20 wherein the primer layer has a functionally suitable for crosslinking with the coating.
22. An apparatus as in Claim 21 wherein the primer layer has a carboxyl functionality.
23. An apparatus as in Claim 22 wherein the primer layer comprises ethylene acrylic acid.
24. An apparatus as in Claim 14 wherein the coating additionally comprises a crosslinking agent for the urethane.
25. An apparatus as in Claim 24 wherein the crosslinking agent comprises a polyfunctional aziridine.