CA2178368C

CA2178368C - Lubricious coatings containing polymers with vinyl and carboxylic acid moieties

Info

Publication number: CA2178368C
Application number: CA002178368A
Authority: CA
Inventors: You-Ling Fan; Lawrence Marlin; Lisa M. Bouldin; Isabel Maria Marino
Original assignee: Union Carbide Chemicals and Plastics Technology LLC
Current assignee: Union Carbide Chemicals and Plastics Technology LLC
Priority date: 1995-06-07
Filing date: 1996-06-06
Publication date: 2000-10-10
Anticipated expiration: 2016-06-06
Also published as: EP0747071B1; US5731087A; MY113807A; ES2164843T3; ATE210471T1; DE69617800T2; DE69617800D1; EP0747071A1; BR9602648A; CA2178368A1; JP3285311B2; JPH08337758A

Abstract

Lubricious coatings comprising a binder polymer having a vinyl moiety and a carboxylic acid moiety and a hydrophilic polymer are disclosed. The coatings can be applied to a variety of substrates such as, for example, catheters, stents, dilatation balloons, guide wires, endotracheal tubes, instruments, implants and other biomedical devices and can provide exceptional lubricity and abrasion resistance.
Processes for applying the lubricious coatings in either one or two coating steps are also disclosed.

Description

LUBEICIOUS COATINGS CONIAINING POLY
WI~ V~YL AND CARBO~YLIC ACn) MOl~;l~;S
.

Fiel-l of thè ~nvantion This iinvention relateæ to lubricious coAt~n~ for . ubstrates such as, for ~Y~n~le, hiome-licAl de-vices. More spe(ifi~lly~ the present invention r~lates to lllhricious CoAI;.-~ cc-.t~;..;.~g a Ly~olJhilic polynner wh ch is lubricious in an aqueous e~lvilo.. Rnt, and a binder poly-mer to -.dhere the LyLo~hilic polymer to the substrate.

~a-.kQrouLd of th~ ~nvention A va~ety of lubricious coA~;ngæ have been proposed for use on hiome-lic~l ~evices such as, for eY~mple, catheters, guide wires, endotrache~ tubes and implAntQ. Commnn _aterials used in the art to provide lLbricious coAtings for hiome-lical devices include, for e~mple, oil, silicone and polymeric materiA~s, such as polyN-vhlyl~ylloli~one, hydrophilic polyureth~nes, Teflon, polyethylene oxide and polyacrJlic acid. Among the most c~mmnn materials used to provide lllh~^ious coAtin~s are hydrophilic polymers which are covalently h~nlietl to the substrate with a binder polymer having reactive filn~*onAl groups, e.g., isocyanate, aldehyde and epoxy groups.
Although th ~ use of such binder polymers having reactive functional groups is ef~ective to provide lubricious co~tingæ having a high degree of abrasion -esistance, such binder polymers are often highly reactive, toxic and ty~ically require special h~n~ling techniques in order to avoid potenial health, safety and ellvil o- --.~nt~l problems.
Acco, ~illgly, new i~ uved lubricious co~tings are desired which utilize bind~r polymers which are less to~c than those which cont~in highly reac~ve functional groups, such as isocyanates, yet which can provide a hi h degree of lubricity and abrasion resistance.

~178368 ~nmm~ ve~ ion In acc ~rdance with the present invention, i~ oved ltlhricious co~tin~ are pro-vided for use on hiQmP!~ic~l devices such as, for eY~mrle~ c~hete-s, guide wires, endotrachael tubes, balloons and impl~nt$. T e coAt;ng~c- have a Ly~o~hilic polymer which is s~lhst~nt;~lly more lllhricious when wetted with an aqueous liquid than when dry, and a binder polymer which is capable of b~n-lin~ to the surface ofthe biome~ic~l device and the hy~o~ ilic polymer. The binder poly~ers suitable for use in accordance with the present invention are copolymers which cv ~l;se a vinyl moiety, preferably vinyl chlori~e or vinyl acetate, and a carboxylic acid moiety.
By the present inVçnt;on, it is now ros.cihle to provide lubricious co?~t;ngS for ~ubstrates which can provide e~cel,lional lubricity and abrasion res stance without the need for using highly reactive, to~ic chemicals to covalently bond the hydrophilic polymer to the surface of the substrate.

net~ d n~ ;--tion of the ~nv~ntion The b nder polymers suitable for use in accordance with the present inve~tion are copolymers, i.e., polymers made from two or more monon ers, which co~ ;se at least one vinyl moiety and at least one carbo~y] ic acid moiety. The vinyl moiety and the carboxylic acid moiety can be present in the same monomer or in different monomers.
The v nyl moiety can be derived from any monomer having a vinyl group uch as, for e~mple, commonly found in compounds such as vinyl chlcride, vinyl acetate and simil?~r esters. r~e~elably, the vinyl moiety has t le formula (CH2=CH-). Typically, the mnnom~rs which cQn~in the ~inyl moiety cv~ ;se from about 2 to 20 carbon atoms per molecule, more often from about 2 to 8 carbon atoms per molecule.
Such vinyl ~nomers may cQnt~in one or more, e.g., 2 or 3, vinyl groups per molecule. Preferably, the vinyl mnnom~r is water-insoluble.
Without bei~g bound to any particular theory, it is believed that polymeric rr nie*es derived from water-insoluble vinyl mnn()mers can provide enh-nrie~ hesiorl ofthe binder polymers to sul~slldtes as comr~red tc water-soluble vinyl mnnomp~rs. As used herein, the term "water-soluble" me~na that at least a 10 weight ~elcellt ("wt. %") solution of the mnnnm~sr is soluble in water.
F.Y~nlples of vinyl monnmers which _ay be s~ hle for use in accordance ~vith the present i~ve~lion include, without lilllitation, vinyl halide-, e.g., vinyl chloride, vinyl flllori-le, -vinyl bro_ide, vinyl trichloride; vinyl ethers, e.g., vinyl ethyl ether, vinyl butyl ether, vinyl ethylhexyl ~ther; vinyl esters, e.g., vinyl acetate, vinyl butarate, vinyl stearate, vil yl propion~te, vinyl ethylhPYon~te; vinyl methyl ketone, vinyl acetyl~ne, bllt~liPne, vinyl ~qlr,nhol (prollncerl in situ through hydrolysis c f vinyl ~cet~te moieties in the polymer) and vinylidene compounds. Vinyl h~ lPs, including vinyl chloride, vinyl _uoride and vinyl bromide, are l,lefelled vinyl monomPrs for use in accordance with the presentinvention.` Vinyl chloride is an especiaIly l refelled monomer for use in accordance with the present invention. Vinyl ester monnmers~ and in particular vinyl acetate, are also ~lefelled for use in accordance ~ith the present invention. Comhin~tions of vinyl halides and vinyl e ters, e.g., vinyl chloride and vinyl acetate, are especially preferred.
The total cnncentration of vinyl monomers in the binder polymer is typically ~rom about 10 to 99.9 mole %, preferably from about 50 to 99.5 mole ~, and, more l,lefelably, from about 70 to 99 mole %. The selection of ?articular vinyl mor omers and their proportions in the binder poly~ er should be selected in order to provide enh~nce~l bon~ing to ~he surface of the substrate to be co~tetl. For inst~nre, a vinyl mono~er that is i~ntir~l or subst~n~i~lly ~imil~r, or comp~t;ble to one or more monQmeric repeating units present in the substrate is preferred t~ provide Pnh~nretl physical bonding between the polymer binder and ;he substrate. More than one vinyl monomtsr may be used.
Further det~ils concerning the selection and amounts of the vinyl monomp~rs are known to those EkilleA in the art. In addition, such vinyl monotnp~rs are commçrcially available.
- The carbo_ylic acid moiety can be denved from any organic acid cont~inin~ a c~bo~yl group. Typically, the carboYylic acids cont~in from 1 to al ,out 26, more typically, from 1 to 8 carbon atoms per molecllle. l'lefellad carbo_ylic acids include, but are not limited to, acrylic, mpllh~crylic~ maleic, it~cQnic, fumaric, and the like. Other carboYylic s,cids such as, for eY~mrle~ lm.~qt... ated fatty acids, and polymerizable arom~tic and alicyclic carboYylic acids may also be employed. ~n addition to the above-m~ntioneA carboYylic acids, the corresponAlng anhydrides, e.g., maleic anhydride, may also be used, provided that the anhydride is hydrolyzed to its acid form in order to promote bQn-ling of the hydrophilic polymer. Otherwise, inferior abrasion re~istance may result. The carboYylic acid groups may be present in their free acid form or partially neutralized, provided that there is a s~fflriPnt amount of free acid to promote bonAing between the hydrop~ilic polymer and the binder polymer.
The -otal conr~n~ation of the carboYylic-cont~ining mo~omPr in the binder ~olymer typically ranges from about 0.1 to 20 mole % and, - preferably, from about 0.5 to 5 mole %. The amount of carboYylic acid monomer s~ould be selecteA in order to provide çnh~nreA bon~ing of the hydrophilic polymer to the binder polymer and substrate. Further details concerning the selection and amounts of the carboYylic acid-cont~ining nnnomPrs are known to those skilled in the art. In addition, sLch carboxylic acid monomPrs are commPrcially available.
In a~dition to the vinyl and carboxyl-cont~ining mnnomers defined abcve, one or more other monomPrs can be used as additional monnmers n the binder polymers of the present invention. Such additional ~onomçrs may be introduced, for e~mrle, in order to provide desired physical, merh~nical or rhemic~l properties to the binder poly~ner, e.g., solubility, process~hility, meltirlg temr~rature, glass trans tion tempela~ e~ hardness, tensile strength and the like.

FY~ les ofthese monomers in~ e isoprene, Ly~o2~yelhyl acrylate, alpha-meth~l styrene, propylene, ethyl acrylate, methyl m~tl-~rrylate, slllfnn~te~ acrylates, and the like.
r~efe~ably, the selec1;on -and amounts of mnnnmars used to prepare the ~inder polyiners of the present invention are effective to provide a binder polymer having the desired degree of ~h~sil n and flPYikility w~en applied to the sul)sl~,ate. Certain binder polymers may be more effe :tive on C~l l~ substrates than on others. Further details concerning t~e selection and amounts of the monom.ors used to make the binder p~lymers are known to those skilled in the art. In addition, it is preferr~d that the binder polymers of the present invention have a molecular weight of from about 5,000 to 1,000,000, more ~refelably from about 20,000 to 500,000 and most preferably from about 20,000 to 100,000 gra~ per gram mole. As used herein, the term "molecular weight" me~ns number average molecular weight. Techniques for determinin the number average molec~ r weight are known to those skilled in th~ art.
Typical copolymers suitable for use as binder polymers in accordance ~vith the present invention include, but are not limited to, maleic acid- Iinyl chloride-vinyl acetate, acrylic acid-vinyl chloride-vinyl acetat~, maleic acid-vinyl chloride-vinyl acetate-vinyl alcohol, acrylic acid--tyrene-vinyl acetate, maleic acid-vinyl ether, and acrylic acid-styrene~butadiene polymers. These polymers may be polymerized in a r~ntlom block or grafted polymer form. Further details concerning t le preparation of such copolymers are known to those skilled in th ~ art. In addition, many of the copolymers described above are commerl ially available from a variety of sources.
The L ~L~J~hilic polymers suitable for use in accordance with the present inv~ntion are any water-soluble or water-swellable polymers which are SLl~S~ lly more lubricious when wetted with an aqueous liquid than ~vhen dry. As used herein, the term "water-swellable"
me~n~ a subst~n~i~lly hydrophilic polymer which, even though is not D-17346 2178~68 soluble in water, would absorb sllffi~Pnt water to render it lllbri~ious in the hydr~ted state. In addition, the term "Lyd~olJhilic" as used herein mea~s that water droplets do not readily form beads on the surface of such Ly~o~hilic m~tçri~l, but instead, the water droplets tend to ass~me a cont~ct angle of less than 45 and readily æpread on its surface.
~ efe led hydrophilic polymers include, but are not limite-l to, those select~d from the group consisting of polyvinyl compounds, polys~cch~r des, polyureth~nes, polyacrylates, polyacryl~mi~es, polyalkylen~ oxides, and copolymers, complexes, mi~tllres~ and del;v~tives thereof. PolyN-vinyl l~ct~m.~ are yrefe~ed polyvinyl compounds for use in accordance with the present invention The term "polyN-vinyl l~ct~m" as used herein m~ns homopolymers and copolymers ~f such N-vinyl l~ct~mc as N-villyl~yl,olitlone, N-vinylbutyro ~rt7.m, N-vinylcaprol~ct~m, and the like, as well as the foregoing prepared with minor amounts, for eY~mple, up to about 20 weight perc-~nt, of one or a ~ ule of other vinyl monQmers copolymerizsble with the N-vinyl l~ct~m~ Of the polyN-vinyl ls~rt~m the polyN-v nylpyrroli~one homopolymers are preferred. A variety of polyN-vinylpyrrolidones are commercially available and of these a polyN-vinylpyrrolidone having a K-value of at least about 30 is especially preferred; The K valve is a measure of molecular weight, the details of which are known to those skilled in the art. Other preferred L~ ~ol,hilic polymers for use in accordance with the present invention in clude, but are not limited to, those selecte-l from the group consisting o ~ N-vinyl~yll olidone-LyL o~yet~yl acrylate copolymers, carbo~ymet~ylcellulose, Ly~o~yetLyl cellulose, poly~cryls-mi~, polyhyLo~ ethyl-acrylate, cationically-modified hy~Lc~yelLylcellulose, polyacrylic ~cid, polyethylene oYi-les, and complexes, ..-;x(-.. es, and del;va~ives-hereo EspeciallypreferredarepolyN-vinyl~yl,~ one, polyethylenf oYille and cellulosics, such as, for e~mple, carboxymet~ylcellulose and c~tionic~lly modified cellulose.

D-17346 ~ 2178368 The L~Lv~hilic polymers sltit~thle for use in accordance with the present inv~ntion can be nr)nionic, cationic, stnionic or stmrhr)teriC.
Typically, t~e molecular weight of the LyLvllhilic polymers is from about 100,0 ~0 to 10,000,000 grams per gram mole, preferably from about 200,0l~0 to 5,000,000 grams per gram mole, and, more ~,efelably, from about "00,000 to 2,000,000 grams per gram mole. Further details concerning t~le ~lel aldtion and s~-lect~on of hydrophilic polymers suitable for 1se in accordance with the present invention are known to those skiller in the art. Such Lydro~hilic polymers are readily cnmm~rcially av~ilSlhle from a vanety of sources such as, for ç~mrle, Union Carbide CoIporation, Danbury, Ct.
It is p~eferred in accordance with the present illvelllion that the hydrophilic ~olymer is bonded to the binder polymer by hydrogen or ionic bonds. While not neceæss~ry for practicing this invention, there may be som6. degree of covalent bon-linE between the binder polymer and the hyd-ophilic poly ler. Howt ve~, ~lefe.dbly, there is a subst~nti~l ~.bsence, i.e., less than about 5%, more l,;efela~bly less than about 1%, of covalent bonds between the binder polymer and the hydrophilic ?olymer based on the total number of bontlinE sites between the binder polymer and the hyLolJllilic polymer. It is also ~lefelled that there is a subst~nti~l absence, i.e., less than about 5%, more preferably less than about 1%, of highly reactive function~ql moieties selPcted from the group consisting of isocyanate, aldehyde and epoxy moiet~ies in the binder polymer.
In addition to the binder polymers and the hyL~hilic polymers, the lubricio~ s co~;ng~ of the present il~velltion may coll-plise one or more additives normally used in co~tinE form~ tion~ such as, for ~Y~mrle~ sll~ct~nts, presel ./~lives, viscosity modifiers, pigments, dyes, and other additives known to those skilled in the art.
Additionally other func~ion~l additives which are ionically bonded to the hydroph lic polymer may also be used. These addit*es include ingredients ~uch as, for çy~mrle~ therapeutic agents, anlilLlo.llbogenic .

D-17346 ~17836g agents, ~ntinicrobial agents and ~nhhintic agents. When ionic additives arq employed in the co~t;ng~ e.g., heparin, which is anionic, it is 1~l efel~ed to use a c~t;onic LyL~lJhilic polymer, e.g., a cs~*or~ lly-modified hyd~v~yethylcellulose. ~imil5~rly, when an additive is c~honic, it i - ~,e~e,~ed to use an anionic Ly~o~hilic polymer, e.g., a polyacrylic ~cid-acryl~mi~e polymer. When an ~ntimi~robial agent such as 2,4,~ tricloro-2'-chloro~y.l;~JhPnyl ether is u3ed as an additive, either an ionic or nonionic Ly l,o~hilic polymer may be employed. The comhin~ior of an additive and a LyLo~hilic polymer may be varied as nee~e~ to provide the desired perform~nre.
The substrates to which the lubricious co~tin~ of the present invention c~in be applied are not limited. The substances which are usable for t~le substrates include, but are not limited to, various organic polymeric compounds such as, for eY~mple, polyami`des, polyesters, ~.g., polyethylene terepht~ te- and poly~lyle:.le - terephth~l~ e, polyvinyl chloride, polyvinylidene chloride, poly~lyl~-le, polyacrylic ~sters, polymethylmethacrylate and other pol~meth~ylic esters, poly;~crylonitrile, polyethylene, poly~lo~ylene, polyurethane, polyvinyl ac~tate, silicone resins, polycarbonate, polysulfone, polybutadie:le-styrene copolymers, polyisoprene, nylon, polyethylene, poly~lo~ylene, polyl ulylene, halog~n~te-l polyolefins, various latexes, various copolymers, various derivatives and blends thereof, and various ino~ganic and metallic substances such as, for çY~mple, glass, ce.d~.ics, stainless steel, and a super elastic metal or shape m~mnry alloys such ~s Ni-Ti alloy, for çY~mple. Typical substrates to which the lubricious c~.atings of the present invention can be applied include, but are not limi-e~ to, catheters, balloon catheters, guide wires, endotracheal tubes, impl~nts and other biomerlic~l devices such as, for çY~mrle, th~ outer surface of an endoscope.
- The lubricious coAtings of the present invention may be applied by either a ~wo-step co~ting process or a one-step co~t;ng process. In a two-step CQ- ting process, the portion of the substrate to be coated is g -first coated with the binder polymer and subsequently coated with the Ly~ hilic polymer. In a one-step co~t;ng process, the binder polymer and Ly~()~}ilic polymer are applied to the substrate in a single step.
Any ~llvellional liquid co~t;ng processes may be ~ 7~e~ in ac~,dance ~iththe presentinv~nt;on Such~.ocesses include, for eY~mple, dip-co~t;ng, spray-co~t;ng, knife-co~ ng and roller co~qt;ng.
Dip-coating is a preferred co~t;ng method in accordance with the present inv~ntion.
In the coating processes of the present invention, the binder polymers and the hydrophilic polymers may be delivered from liquids contained ir either a solution, a dispersion or an çmlll~ion of the polymers. Il the one-step coiq~;ng methods, the binder polymers and the hydroplilic polymers are cont~ine-l in the s~me liquid medium. In the two-step methods, the binder polymers and the hydrophilic polymers arD, cont~ine-l in separate liquid mediums. A-lllit;on~l co~ting step - may also be employed to introduce different poly-mers or additives. The liquid mediums used for delivering the bi~der polymers and hydrop~nilic polymers may be organic, aqueous or an organic-aqueous ~e. The liquid medium used for delivering the binder polymer can be selected so that it has some solvency for the substrate, i.e., when the substrate is polymeric. This can enh~nce the adhesion between th~ binder polymer and the substrate and aid to the film formation o `the co2st;ng material. r~efelled liquid mediums for delivering t~e binder polymers and hydrophilic polymers include, but are not limi ~-1 to, esters, e.g., ethyl ~cet~te, iso~ Jyl acetate; alcohol~, e.g., isol.lo~l alcohol, e~nol, butanol; ketones, e.g., acetone, methylethy~ketone"li~cetone ~lcohol, methyl isobutyl ketone; amides such as dim thyl form~mi~l~; toluene; glycol ethers such as butyl glycol ether; chlor nated solvents such as dichloroethane, water, and ~lules th ~reof. r~efelably, the liquid mediums are selected so that the binder polymers and llyL~lJhilic polymer evenly wet the surface of the substra-e to be coated.
-.
r~ef~ably, the conr~ntration of the binder polymer and the hydrophilic polymers in the liquid me~ m~ are snffi~nt to provide the desired smounts of the respective polymers in the lnhrir-iouæ
co~t;n~. Typically, the concantration ofthe binder polymers in the liquid medi~m will range from about 0.05 to 10 weight ~elcellt and, l"~efe~ably, -`rom about 0.2 to 2 weight percent based on the total weight of tbe liquid medium. Typically, the a~nrantration of the Lyd~o~hilicpolymers will range from about 0.1 to 20 weight percent and, ~l efel .bly, from about 0.5 to 5 weight percent, based upon the total weight of the liquid medium. Further details concerning the selection of iquid medillms for delivering the binder polymers and hydrophilic polymers of the present invention are known to those skilled in t~ e art.
The oo~ting processes of the present invention are preferably conducted i~ a liquid phase at atmospheric pressure and at a temperature from about 20 to 90C. The resitl.once times for cont~cting the surface ~f the substrate to be coated with the liquid mediums con~ining ~he binder polymer or the hydrophilic polymer, or both, range from about 1 second to 30 minukes, preferably from about 10 secontl~ to W minukes. It is generally desirable to dry the co~tings after app~ic~tion of the coating at a temperature from about 30 to 150C, pref~`rably in a forced-air oven. Microw~ve ovens and jnfrared heaters maV also be used if desired. Typical drying times range from about 1 miruke ko 24 hours and preferably range from about 10 minutes ko ~ hours. When a two-step co~ting process is employed, it is ~efel,ed k dry the binder polymer before application of the hydrophilic polymer.
The 1 lbricious co~;ng~ which result from the cQ?~ting processes of the prese~t invention typically have a t~liçkness of from about 0.05 to 10 microns, and preferably from about 0.1 ko about 5 microns. When a two-step ooating process is employed, the resulting co~ting l lefelably comprises a inner layer which is rich, i.e., greater than 50%, in the ~178368 binder poly~per which con~ctS the surface of the substrate, and an outer layer ~hich is rich, i.e., greater than 50%, in the hydrophilic polymer whi~h cont~tcts the inner layer. The outer layer, which is rich in the hydroohilic polymer, has an outer surface which hecomes lubricious w~en exposed to an aqueous liquid. When a one-step coS~t;ng proc ss is employed, the resulting coat~ng C~ es a single layer which s l,lefe,ably a subs~ ..t;slly homogeneous ..-; Y ~--. e of the binder poly ~er and the LyLo~hilic polymer. HOw~er, since the binder poly~er will often have more ~ily for the substrate than the hydrophilic 2olymer, it is believed that there may be a higher concçn~atic 1 of the binder polymer near the surface of the substrate.
The following ~stmples are presented for illu~La~ive purposes and are not ntentlell to limit the scope of the claims which follow.

~n~les The f~llowing tests were employed in conducting the ç~s mrles.
Cont~ct Angle Test: The cont~ ct angle of distilled ~ater on either coate~l or 1lnco~terl substrate was measured using a NRL
Contact Ande Goniometer Model A-100( Rame'-hart, Inc., Mo11ntain Lakes, N. J. ) at room temperature. The average value of three -measuremeLts was used.
Coçffi ~er t of Friction Test: A pair of catheters is laid parallel to each othe ~ on a hori7.ont~1 stainless steel platfor~ at a distance of about 1.5 inches apart. The platform and the catheters are subsequentl ~ wetted thoroughly with about 100 milliliters ("ml") of distilled wa~er. A rectangular shaped aluminum block (2g2g3 inches) weighing 10~ grams (ng") wrapped in a wet cellulose acetate m~mhrane is placed on ,op of the catheters at the free-moving end of the pla~rol~.
Thereafter, -,he platform is raised gradually and steadily from the free-moving end mtil an inc1in~tion angle 0 is rea~-he~l where the block begins to sli le on the wet catheter surfaces. The coçffi~içnt of friction (nCOF") is c~.lclll~te-l as tangent 0.

Abra~ion Test - The abrasion resistance of the wet co~ting is measured ~;y abrading the wet c~thPter through a silicQne elastomer o~et(t~.e inside diameter of the ~.~...---Pt is made to be about 10%
~m~llçr th~ the outside diameter of the ~t~eter) for 100 abr~ions, i.e., strokes. Each abrasion consists of a comrlete back and forth traveling of the catheter through the ~ ~o~.. et~ The COF of the abraded c~het~r is measured again and reported as the COF after abrasion.

The following ingredients were used in conducting the ç~mples. .~11 of the ingre~ien~Q used in the F~ mples are commPrcial y available from a variety of sources.

PVC - polyvinyl chloride PVC endot~P~he~l tubes - 32 French size.
IPA - iso~ yl ~lcohol~
Gantrez~ AN119 - a methyl vinyl ether-maleic anhydride copolymer having a molecular weight of 20,000 grams per gr~m mole, available from ISP T~chnology, Wayne, N.J.
MEK - met~yl ethyl ketone.
PVP - poly~-vinylpyrrolidone having a K-valve of K-90.
CMC - Carboxymethyl cellulose having a molecular weight of about 250,000 grams per gram mole available as 99-7M8SXF from Aqualon C~mpany, Willmin~ton, DE.
DAA- Di~c-~tcne alcohol.
PVC drain ~.ubes - 20 French size Carboxyl V'nyl Resin-I - a vinyl-chloride-vinyl acetate maleic acid (81-17-2 weight %) copolymer having a molecular weight of 15,000 grams per gram m~le.
Carboxyl V hyl Chlorifle Resin-II - a vinyl-chloride-vinyl acetate-maleic acid (83-16-1 weight %) copolymer having a molecular weight of 19,000 grams per 8ram mole.
~ .

D-17346 ~178368 Carboxyl Vi~yl Chloride Resin-III - a vinyl chlori~e-vinyl acetate-LyL~yall~l acrylate-carboxyl-cQ..t~;..;..g copolymer, having a moleclll~r weight of 26,000 grams per gram mole av~ hle as Bakelite Waterborne Solution Vinyl AW875 from Union Carbide Corporation, Danbury, C''.
Tygon~) tub ng - 0.25 inch ID, 0.375 inch OD.
C~t;onic HEC1 - a quaternized hy~Lo~yethyl celllllose having a molar and degree ~f substitution of 2.3 and 1.85 ,respectively, and a molecular ~eight of 750,000 grams per gram mole.
Cationic HE C2- a qll~terni7.erl hy~o~yethyl cellulose having a molar and degree of substitution of 2.3 and 1.85, respectively, and a moleclll~r v eight of 300,000 grams per gram mole PET - polye-hylene terephth~l~te balloon catheters.
Polyethylen ~ balloons - 2.5 cm dilatation balloons.
PET ballooLs - 6.5 cm ~ t~t;on balloons.
Butyl glycol ether - ethylene glycol monobutyl ether.
.
In the FY~mples, two substrates were used for each test because the Coeffici~nt of Friction Test requires two substrates to be run in parallel. O Ie of t_e substrates was used for the Contact Angle Test, and an aver~ge of three re~ing~ is reported.

F.~mple C-1 One ;~air of PVC Tygon tubes were wiped with a tissue conhining -PA and air dried for 10 minlltes ("min."). The clean tubes were dippec~ in an 1% solution of Galltlt:~) AN119 in MEK for 10 Eecon~l~ ("sl~ c.") and followed by drying in a forced air oven at 90C for 30 mimltes. The tubes were then dipped into a 2 wt~ solution of PVP
in an IPA/v~ater (70/30 wt%) .. .; x ~ ~. . e for 1 minllt~ and followed by drying in a ~orced-air oven at 90C for 1 hour. The coated tube had a water cont~t angle of 16. The coated tube was lubricious initially, but the lub}icity was lost imme~ qtely upon toll-~-hing showing a lack of durability. ''.his F~mrle i~mon~trates that despite the presence of the vinyl mciety, the lack of the carboxylic acid moiety in the binder polymer pro rided a co~ting with inferior abrasion resist~nc~.

F.~mp]e 2 Exam~ole 1 was repeated with the exception that after the PVC
Tygon tubes were coated with the first coAtin~ solution and dried at 90 C for 30 ~hin they were so~ke~l in distilled water overnight before the second c~ting was applied in order to promote the hydrolysis of the anhydride groups to carboxylic acid groups. The coated tubes were lubricious iritially and gradually lost their lubricity after 100 abrasions a evi-lence-l by the following data:

.~m~lq Contact An~le Coefficient of Fnction Before Abrasion After Abrasion 2 32 0.12 0.45 Uncoate 1 77 0.5 0.5 Quite surprisingly, the co~ting of this F,~mple 2 appeared to be more durabl - than that in the F.~mple 1 since there was only a gradual red~ ction in lubricity. Moreover, the coated tube showed no apparent lu~)ricity reAllctioIl during the early stage of Abrasion Test.
Thus, the data from this F.~mple 2 riemon~trate~ quite sulprisingly, that the pre ence of carbogylic acid groups, which were present as a result of hydrolysis of the ~nhydride groups in the binder polymer, enhS~nrel3 th ~ abrasion resistance of the co~ting as compared to the co~tin~ of F,-~mple 1, which cont~ined a vinyl moiety, but no carbogylic acid moiety.

mple C-~
Two pieces of PVC endotracheal tubes were wiped with a tissue cnnt~inin~ r.'A, air dried, and subsequently dipped in a 2 wt% PVP
solution in diacetone ~lcohnl for 5 min. The tubes were dried in a forced air oven at 90-C for 2.5 hours. The fini~herl co~t;ng was lubricious ~ut slimy. Lubricity was lost rapidly upon touching, and essentially s~ll coAt;ng was removed from the tubes after abrasion.

Sample Contact An~le Coefficient of Friction Before Abrasion After Abrasion C-3 14 0.05 0.21 Uncoated ~ 80 0.25 0.25 .
mple C-L ..
~ rle C-3 was repeiqterl with the exception that a coating solution co, ~ g 0.2 wt% of vinyl chloride resin I in diacetone alcohol was -1sed. The fini~hed coating showed a moderate increase in hydrophilici~y but was not lubricious in water. The Abrasion Resistance '~est was not conducted.
~am~le Contact Anple Coefficient of Friction Before Abrasion C-4 58 0.25 Unco~terl 80 0.25 ples C-3 and C-4 illustrate that neither a Lyd~ hilic polymer no~ a vinyl polymer alone is sllffi~çnt to provide an adherent lubricious c~ ;ng D-17346 2178~68 .

.

F.lr~mrle 5.
- Two ~ ieces of PVC drain tubes were rle~neA with IPA and air dried. The ~leaned tubes were dipped in an 1wt% sohlll;on of carbogyl vinyl chloIi~e resin-I in ethyl acetate for 30 sec. and followed by drying in a forced aCr oven at 90C for 30 min. The dried tubes were then dipped in a _wt% solution of PVP in a water/IPA ...; ~ .. e (57/43 wt.%) for 30 sec. and followed by drying in a forced air oven at 90C for 1 hour ('~r"). The fini~cheA co~ing was ---;fo~ ..., optically clear in both the dry or llJ~Lated state, and very lubricious upon exposure to water.
The contact ~ngles with water were measured to be 66 and 10 for the llnro~ted a~ d coated tubes showing a high degree of hydrophilicity of the coated s lrfaces. The coefficient of fric~;on measured in the presence of vater for the nnco~teA and coated tubes was 0.32 and 0.15, respectively, showing a significant reAllct;on in fric1;on The wet tubes were subsec uently abraded against an elastomer ~ et for 100 times and tl .e coefficient of friction remeasured. The valu~e was 0.21 which was sill subst~n~lly lower than that of the nnco~t~d tubes.

- F,~mple 6.
F.~ rple 5 was repeated with the exception that a 2 wt % PVP
solution ins-ead of 1 wt % solution was used. The fini.she~l coating was uniform, op ically clear, and lubricious upon h~dldlion. The contact angle measured in water was 13. The coçfficient of friction before and after 100 abrasions were found to be 0.15 and 0.19, respectively.

mple 7.
F,~rr ple 5 was repeated with the e~cel tion that an 0.5wt%
solution of carboxyl vinyl chloride resin-II in ethyl acetate and a 2.5wt% solu ;ion of PVP in a ~ule of IPA/diacetone alcohol(50/5~wt%) were used. The ~ni~heA co~tin~ was ....ifo~....
optir~lly cle~r, and lubricious upon hydration. The coI t~ct angle !~ ~

measured ~ith water was 35, and the coefficient of friction measured before and fter 100 abrasions was 0.03 and 0.09, respectively.

h:x~ .le 8.
Sections of Tygon tubing were cleaned with IPA and air dried.
The tubing -ec~ione were dipped in a 1wt% call,o~yl vinyl chlo~ide resin-I solu-ion in ethyl ~cet~te for 30 sec. and followed by drying in a forced air oven at 90C for 30 min. The tubing sections were then dipped into ~n 0.5wt% cationic HEC solution (50/50 wt% blend of ç~tioniC HE''1 and c~tionic HEC2) in a solvent ~ e consisting of 95/5 weight % of water/IPA for 30 sec. and followed by dr~ing at 90C
for one houl . The fini.ehed co~ting was l~..;fol~, optically clear in both the dry and wet state, and very lubricious upon hydration. Contact angles with water for the lmco~te~ and coated tubing were 76 and 10, respectively, showing a high degree of hydrophilicity of the coated surfaces. I~e coefficient of friction before and after 100 abrasions for the llnco~te 1 and coated tubing were found to be 0.68 /0.6,8 and 0.1/0.03, re-pectively.

F,~mple 9.
- - Twelv~e inch ~ectione of a polyethylene catheter were cleaned with IPA ar d air dried. The catheters were dipped into a 1wt%
solution of carbo~yl vinyl chloride resin-I in ethyl acetate for 30 séc.
and followe~ by dr~ing in a forced air oven at 65C for one hour. The catheters w-re subsequently dipped in a 0.5wt% cationic HEC (same compositior as used in h:Y~mrle 8) solution for 30 sec. and followed by drying in a 'orced air oven at 65C for 2 hrs. The co~ting was .~..;fo and smooth The coeffi~içnt of friction for the uncoated and coated catheters w~re measured to be 0.86 and 0.27, respectively.

- D-17346 , 217~368 ' F.~ .le 10 Poly~ thylene h~lloon.e were cleaned with IPA and air dried. The balloons w~re than coated with a 1wt% solution of c~.l)o,~yl vinyl chloride resin-I in ethyl ~qcet~te, by dipping-for 30 sec. The balloons were allowed to dry in a forced air oven at 65 C for 1 hour, and were subsequentpy dipped in a 0.5 wt. % c~tionic HEC solution (same composition asused in h~Y~mrle 8) for 30 sec. A 2-hour forced-air oven dry at 65C followed. The co~;ng.e obtained were smooth and very lubricious ~hen wet. A coated balloon was dipped into a solution cont~ining 500 units per I of heparin for 1 minl~te and air dried. The presence of i_mobili7.e-1 heparin in the co2ting was col~ed by infrared sp~ct,roscopy.

mrle 11.
PET balloons were cleaned with IPA and air dried. The balloons~
were than ~ oated with a 1wt% solution of carboxy vinyl chloride resin-I
in ethyl acPtate, by dipping 1 min. The balloons were allQwed t,o dry in a forced air oven at 75C, for 30 m in. and were subsequently dipped in a 0.5wt% c~tionic HEC solution (same composit,ion as used in F'.~P~mrle 8) for 1 sec. A 1-hour forced-air oven dr~ at 75C followed. The coatings ob-,ained were smooth and very lubricious when wet. A coat,ed balloon war dipped into a solution cont~ining 500 units per ml of heparin for 1 _inute and air dried. The presence of immobilized heparin in he cQ~t;n~ was confirmed by infrared spectroscopy.

h~Y~mples 12 13.
A 1wc% solution of carboxyl vinyl chloride resin-I solution in rli~cet~ne ~ cohol was prepared by mi~ing in a Waring blender for about 10 m n. to give a clear solution having a Brookfield viscosity of 8 centipoises(~'cP"). A 2.5 wt% solution of PVP in diacetone alcohol was prepared ir the same m~nn~r to give a clear solution having a Brool~ield l~iscosity Of 36 cP. The two solutions were comhine~ in the ..

D-17346 217~36&

weight ratiqs of 2/1 and 4/1 to yield solutions c~nt~ining ~li~elellt ratios of the two polymers:

~olution PVP/~esin-Iratio Total ~olids5b Brookfield Vis.. cP

A ~ 2/1 2.0 25 B 4/1 2.2 30 Four ~ieces of PVC endotracheal tubes were cleaned with IPA
and air dried. Two tubes were dipped in Solution A for 30 sec. and followed by drying in a forced air oven at 90C for 2.5 hrs. The other two tubeæ w.3re dipped in Solution B for 30 sec, and followed by drying at 90C for 2.5 hrs. The fini~he-l tubes were uniform, optically clear in both the dry and wet state, and very lubricious upon hydration.
Surface cha-acterizations gave the following results:

~olution l sedContact ArtFleCoefficient of Coefficient of with Water Friction Friction After Abrasion (100 times) Uncoat~d 80 0.25 0.25 A 30 0.14 -0.17 B 22 0.09 0.11 r D-17346 ~178368 .

mples 1~18 One-~ tep co?.ting solutions of carboxyl vinyl chloride resin-I and PVP, at 2.2~o total solids, in diacetone ~lcohol were prepared on a roll mill at va~ing polymer ratios as shown below:

Solution PVP/Resin-I TotalSolids % Brookfield Viscosity. cP.

4/1 2.2 30 2 5/1 2.2 29 3 7/1 2.2 32 4 10/1 2.2 34 PVC endotracheal tubes were coated with the above solutions according tc the following procedure. The tubes were wiped with IPA
and allowec to air dry for 10 min. A pair of the tubes was then dipped into each of the above solutions for a specified time (indicated below) and subseqLently dried in a forced air oven at 90 C for 2.5 hours. The lubricity, b~fore and after 100 abrasions with a silicone elastomer grommet, of the coated tubes was characterized by measuring the coeffi~çnt o ~iction in the presence of water. In addition, the contact angle was a so measured and showed a high degree of hyL o~hilicity for the coat~d tubes.

F.r~m,ple ,qolution niPPeinmgin Coefficient of Friction AConltactO
Before After Abr~ion Abrasion 14 1 5 0.07 0.08 22 ~ 2 0.5 0.09 0.14 22 16 3 2.45 0.09 0.08 22 17 4 0.5 0.09 0.07 23 18 4 5 0.09 0.08 25 Uncoated 0.25 0.2,5 81 Tube F,r~mI)le 19.
A wa~er-borne one-step coating fluid of carboxyl vinyl chloride resin-III an~ PVP, at 2.2% total solids, was prepared in an aqueous medium con ~ining 80% rli~cet~ne alcohol and 20% water. The ratio between PV? and the vinyl resin was 10: 1. The dispersion was uniform anc~ slightly hazy and showed a Brool~ield viscosity of 45 cP.
Two pieces cf PVC endotracheal tubes were coated accoldillg to the same proced~~re described in F~r~mples 14 with a 5 min. dip in the co~ting solu ,ion and followed by a 1.5 hours drying at 90C. The cQ~t;nF was lear and uniform, and was characterized using the same methods des~ibed in Fr~mrles 14.

Sample Contact AnFle. Coefficient of Friction- Before Abrasion After Abrasion Uncoated 80 0.25 0.25 8 ~ 23 0.05 0.06 F~r~mrle 20~
A wat.~r-borne coating formnl~1ion was prepared by mi~ing carboxyl vinyl chloride resin-III and PVP in butyl glycol ether, diacetone altohol, and water, .~lule to give the following composition:
wt%
Carboxyl vinyl chloride resin-III 0.4%
PVP 4%
Butyl Glycol Ether ` 20%
Diacetone A: cohol 20 ~7O
Water 55.6%
Brookfield V`scosity, cP 89 Two pieces o PVC endotracheal tubes were dipped in the above solution for 5 minutes and dried in a forced air oven at 90 C for 1.5 hours. The finished coating was uniform. The contact angle with water was 4~ .7, and coefficient of f~iction in the presence of water was measured to be 0.03 and 0.07 after 100 abrasions with an elastic membrane. The uncoated PVC endotracheal tube showed correspon~lir F values of 80, 0.25, and 0.25, respectively.

F.~qmple 21 Two p~eces of Tygon tubes were coated acco~ g to F.~mple 14 with the exception that the carboxyl vinyl resin-I was replaced with a low molecul~r weight vinyl acetate-acrylic acid copolymer (99.2 wt%

- : 2~7836'~
^ - D-17346 ;

vinyl acetat~ / 0.8 wt% acrylic acid). The coated tubes were lubricious and showed COF before and after 100 abrasions of 0.25 and 0.36, respectively The lmco~te~ tube showed a COF of 0.51. The cont~ct angle with distilled water for the coated and l~nco~te~3 tubes were 10 and 77, re~pectively.

Althcl~gh the invention has been described above with respect to specific asp~cts, those skilled in the art will recognize that other aspects are nten~le-l to be included within the scope of the claims which follo~. For instance, polymers other than the specific binder polymers and hydrophilic polymers may be employed in accordance with the pr~ sent invention. In addition, other carboxylic acids such as, for eY~mple, halide-substituted carboxylic acids such as chlorocetic acids or ami;no acids may be utilized instead of the specific carboxylic acids disclo- ed. Moreover, in addition to the specific vinyl moieties set forth above,~other vin~l moieties such as, for e~mrles~ those found in compounds -uch as vinyl ben7.ene, vinyl toluene, methyl methacrylate and acrylon trile may be used in accordance with the present invention.

Claims

1. In a lubricious coating applied to a surface of a substrate comprising:
(i) a hydrophilic polymer which is substantially more lubricious when wetted with an aqueous liquid than when dry;
and (ii) a binder polymer which is capable of bonding to the surface of the substrate and the hydrophilic polymer;
the improvement wherein (i) the binder polymer is a copolymer comprising vinyl chloride, vinyl acetate and a carboxylic acid and (ii) there is a substantial absence of covalent bonding between the binder polymer and the hydrophilic polymer.

2. The lubricious coating of claim 1 wherein the carboxylic acid comprises from 1 to about 26 carbon atoms per molecule in the acid moiety.

3. The lubricious coating of claim 1 wherein said substrate is selected from the group consisting of polyurethane, polyvinyl chloride, polyacrylate, polycarbonate, polystryrene, polyester resins, polybutadiene-styrene copolymers, nylon, polyethylene, polypropylene, polybutylene, silicon, polyvinyl acetate, polymethacrylate, polysulfone, polyisoprene, copolymers and derivatives thereof, glass, metal, ceramic and mixtures thereof.

4. The lubricious coating of claim 1 wherein the hydrophilic polymer is selected from the group consisting of polyvinyl compounds, polysaccharides, polyurethanes, polyacrylates, polyacrylamides, polyalkyleneoxides and copolymers, complexes, derivatives and mixtures thereof.

5. The lubricious coating of claim 1 which further comprises an additive selected from the group consisting of therapeutic agents, antithrombogenic agents, antimicrobial agents, antibiotics and mixtures thereof.

6. A biomedical device comprising the lubricious coating of claim 1.

7. The biomedical device of claim 6 which is selected from the group consisting of catheters, guide wires, stems, dilatation balloons, endotracheal tubes, instruments, and implants.